Nanomedicine against Alzheimer’s and Parkinson’s Disease

Ankit       Tandon; Sangh    J.   Singh; Rajnish    K.   Chaturvedi
Abstract

Alzheimer’s and Parkinson’s are the two most rampant neurodegenerative disorders worldwide. Existing treatments have a limited effect on the pathophysiology but are unable to fully arrest the progression of the disease. This is due to the inability of these therapeutic molecules to efficiently cross the blood-brain barrier. We discuss how nanotechnology has enabled researchers to develop novel and efficient nano-therapeutics against these diseases. The development of nanotized drug delivery systems has permitted an efficient, site-targeted, and controlled release of drugs in the brain, thereby presenting a revolutionary therapeutic approach. Nanoparticles are also being thoroughly studied and exploited for their role in the efficient and precise diagnosis of neurodegenerative conditions. We summarize the role of different nano-carriers and RNAi-conjugated nanoparticle-based therapeutics for their efficacy in pre-clinical studies. We also discuss the challenges underlying the use of nanomedicine with a focus on their route of administration, concentration, metabolism, and any toxic effects for successful therapeutics in these diseases.
Keywords: Nanomedicine, alzheimer's disease, parkinson's disease, nanoparticles, neurodegenerative disease, apoptosis, neuroinflammation, neurodegenerative disease.
[1] 
Przedborski S, Vila M, Jackson-Lewis V. Neurodegeneration: what is it and where are we? J Clin Invest  2003; 111(1): 3-10.
[http://dx.doi.org/10.1172/JCI200317522] [PMID: 12511579] 
[2] 
Heemels MT. Neurodegenerative diseases. Nature  2016; 539(7628): 179.
[http://dx.doi.org/10.1038/539179a] [PMID: 27830810] 
[3] 
Abeliovich A, Gitler AD. Defects in trafficking bridge Parkinson’s disease pathology and genetics. Nature  2016; 539(7628): 207-16.
[http://dx.doi.org/10.1038/nature20414] [PMID: 27830778] 
[4] 
Canter RG, Penney J, Tsai LH. The road to restoring neural circuits for the treatment of Alzheimer’s disease. Nature  2016; 539(7628): 187-96.
[http://dx.doi.org/10.1038/nature20412] [PMID: 27830780] 
[5] 
Wyss-Coray T. Ageing, neurodegeneration and brain rejuvenation. Nature  2016; 539(7628): 180-6.
[http://dx.doi.org/10.1038/nature20411] [PMID: 27830812] 
[6] 
Crane PK, Doody RS. Donepezil treatment of patients with MCI: a 48-week randomized, placebo- controlled trial. Neurology  2009; 73(18): 1514-5.
[http://dx.doi.org/10.1212/WNL.0b013e3181bd6c25] [PMID: 19884584] 
[7] 
Desai AK, Grossberg GT. Diagnosis and treatment of Alzheimer’s disease. Neurology  2005; 64(12)(Suppl. 3): S34-9.
[http://dx.doi.org/10.1212/WNL.64.12_suppl_3.S34] [PMID: 15994222] 
[8] 
Wagner V, Dullaart A, Bock AK, Zweck A. The emerging nanomedicine landscape. Nat Biotechnol  2006; 24(10): 1211-7.
[http://dx.doi.org/10.1038/nbt1006-1211] [PMID: 17033654] 
[9] 
Etheridge ML, Campbell SA, Erdman AG, Haynes CL, Wolf SM, McCullough J. The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomedicine (Lond)  2013; 9(1): 1-14.
[http://dx.doi.org/10.1016/j.nano.2012.05.013] [PMID: 22684017] 
[10] 
Goldsmith M, Abramovitz L, Peer D. Precision nanomedicine in neurodegenerative diseases. ACS Nano  2014; 8(3): 1958-65.
[http://dx.doi.org/10.1021/nn501292z] [PMID: 24660817] 
[11] 
Agarwal S, Yadav A, Tiwari SK, et al. Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation. J Biol Chem  2016; 291(31): 15923-39.
[http://dx.doi.org/10.1074/jbc.M115.709493] [PMID: 27252377] 
[12] 
Dugger BN, Dickson DW. Pathology of Neurodegenerative Diseases. Cold Spring Harb Perspect Biol  2017; 9(7): 9.
[http://dx.doi.org/10.1101/cshperspect.a028035] [PMID: 28062563] 
[13] 
Dugger BN, Adler CH, Shill HA, et al. Arizona Parkinson’s Disease Consortium. Concomitant pathologies among a spectrum of parkinsonian disorders. Parkinsonism Relat Disord  2014; 20(5): 525-9.
[http://dx.doi.org/10.1016/j.parkreldis.2014.02.012] [PMID: 24637124] 
[14] 
Dugger BN, Hentz JG, Adler CH, et al. Clinicopathological outcomes of prospectively followed normal elderly brain bank volunteers. J Neuropathol Exp Neurol  2014; 73(3): 244-52.
[http://dx.doi.org/10.1097/NEN.0000000000000046] [PMID: 24487796] 
[15] 
Hinz FI, Geschwind DH. Molecular Genetics of Neurodegenerative Dementias. Cold Spring Harb Perspect Biol  2017; 9(4): 9.
[http://dx.doi.org/10.1101/cshperspect.a023705] [PMID: 27940516] 
[16] 
Tcw J, Goate AM. Genetics of β-Amyloid Precursor Protein in Alzheimer’s Disease. Cold Spring Harb Perspect Med  2017; 7(6): 7.
[http://dx.doi.org/10.1101/cshperspect.a024539] [PMID: 28003277] 
[17] 
Han SS, Williams LA, Eggan KC. Constructing and deconstructing stem cell models of neurological disease. Neuron  2011; 70(4): 626-44.
[http://dx.doi.org/10.1016/j.neuron.2011.05.003] [PMID: 21609821] 
[18] 
Marton RM, Paşca SP. Neural Differentiation in the Third Dimension: Generating a Human Midbrain. Cell Stem Cell  2016; 19(2): 145-6.
[http://dx.doi.org/10.1016/j.stem.2016.07.017] [PMID: 27494668] 
[19] 
Paşca AM, Sloan SA, Clarke LE, et al. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat Methods  2015; 12(7): 671-8.
[http://dx.doi.org/10.1038/nmeth.3415] [PMID: 26005811] 
[20] 
About a peculiar disease of the cerebral cortex. By Alois Alzheimer, 1907 (Translated by L. Jarvik and H. Greenson). Alzheimer Dis Assoc Disord  1987; 1(1): 3-8.
[PMID: 3331112] 
[21] 
Maurer K, Volk S, Gerbaldo H, Auguste D. Auguste D and Alzheimer’s disease. Lancet  1997; 349(9064): 1546-9.
[http://dx.doi.org/10.1016/S0140-6736(96)10203-8] [PMID: 9167474] 
[22] 
Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri C P. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement  2013; 9: 63-75.
[23] 
Ott A, Breteler MM, van Harskamp F, et al. Prevalence of Alzheimer’s disease and vascular dementia: association with education. The Rotterdam study. BMJ  1995; 310(6985): 970-3.
[http://dx.doi.org/10.1136/bmj.310.6985.970] [PMID: 7728032] 
[24] 
Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med  2010; 362(4): 329-44.
[http://dx.doi.org/10.1056/NEJMra0909142] [PMID: 20107219] 
[25] 
Holtzman DM, Morris JC, Goate AM. Alzheimer’s disease: the challenge of the second century. Sci Transl Med  2011; 3(77): 77sr1.
[http://dx.doi.org/10.1126/scitranslmed.3002369] [PMID: 21471435] 
[26] 
Reiman EM, Chen K, Alexander GE, et al. Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism. Proc Natl Acad Sci USA  2005; 102(23): 8299-302.
[http://dx.doi.org/10.1073/pnas.0500579102] [PMID: 15932949] 
[27] 
Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol  2011; 10(9): 819-28.
[http://dx.doi.org/10.1016/S1474-4422(11)70072-2] [PMID: 21775213] 
[28] 
Wang J, Gu BJ, Masters CL, Wang YJ. A systemic view of Alzheimer disease - insights from amyloid-β metabolism beyond the brain. Nat Rev Neurol  2017; 13(10): 612-23.
[http://dx.doi.org/10.1038/nrneurol.2017.111] [PMID: 28960209] 
[29] 
Mann DM. Pyramidal nerve cell loss in Alzheimer’s disease. Neurodegeneration  1996; 5(4): 423-7.
[http://dx.doi.org/10.1006/neur.1996.0057] [PMID: 9117557] 
[30] 
Norfray JF, Provenzale JM. Alzheimer’s disease: neuropathologic findings and recent advances in imaging. AJR Am J Roentgenol  2004; 182(1): 3-13.
[http://dx.doi.org/10.2214/ajr.182.1.1820003] [PMID: 14684506] 
[31] 
Selkoe DJ. Alzheimer’s disease is a synaptic failure. Science  2002; 298(5594): 789-91.
[http://dx.doi.org/10.1126/science.1074069] [PMID: 12399581] 
[32] 
Bozoki AC, Korolev IO, Davis NC, Hoisington LA, Berger KL. Disruption of limbic white matter pathways in mild cognitive impairment and Alzheimer’s disease: a DTI/FDG-PET study. Hum Brain Mapp  2012; 33(8): 1792-802.
[http://dx.doi.org/10.1002/hbm.21320] [PMID: 21674695] 
[33] 
Jack CR Jr, Petersen RC, Xu YC, et al. Medial temporal atrophy on MRI in normal aging and very mild Alzheimer’s disease. Neurology  1997; 49(3): 786-94.
[http://dx.doi.org/10.1212/WNL.49.3.786] [PMID: 9305341] 
[34] 
Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol  2011; 70(11): 960-9.
[http://dx.doi.org/10.1097/NEN.0b013e318232a379] [PMID: 22002422] 
[35] 
Beach TG, Monsell SE, Phillips LE, Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010. J Neuropathol Exp Neurol  2012; 71(4): 266-73.
[http://dx.doi.org/10.1097/NEN.0b013e31824b211b] [PMID: 22437338] 
[36] 
Scheltens P, Blennow K, Breteler MM, et al. Alzheimer’s disease. Lancet  2016; 388(10043): 505-17.
[http://dx.doi.org/10.1016/S0140-6736(15)01124-1] [PMID: 26921134] 
[37] 
De Strooper B, Vassar R, Golde T. The secretases: enzymes with therapeutic potential in Alzheimer disease. Nat Rev Neurol  2010; 6(2): 99-107.
[http://dx.doi.org/10.1038/nrneurol.2009.218] [PMID: 20139999] 
[38] 
Tomita T. Secretase inhibitors and modulators for Alzheimer’s disease treatment. Expert Rev Neurother  2009; 9(5): 661-79.
[http://dx.doi.org/10.1586/ern.09.24] [PMID: 19402777] 
[39] 
Wischik CM, Harrington CR, Storey JM. Tau-aggregation inhibitor therapy for Alzheimer’s disease. Biochem Pharmacol  2014; 88(4): 529-39.
[http://dx.doi.org/10.1016/j.bcp.2013.12.008] [PMID: 24361915] 
[40] 
Mullane K, Williams M. Alzheimer’s therapeutics: continued clinical failures question the validity of the amyloid hypothesis-but what lies beyond? Biochem Pharmacol  2013; 85(3): 289-305.
[http://dx.doi.org/10.1016/j.bcp.2012.11.014] [PMID: 23178653] 
[41] 
Selkoe DJ. Resolving controversies on the path to Alzheimer’s therapeutics. Nat Med  2011; 17(9): 1060-5.
[http://dx.doi.org/10.1038/nm.2460] [PMID: 21900936] 
[42] 
Perrin RJ, Fagan AM, Holtzman DM. Multimodal techniques for diagnosis and prognosis of Alzheimer’s disease. Nature  2009; 461(7266): 916-22.
[http://dx.doi.org/10.1038/nature08538] [PMID: 19829371] 
[43] 
Parkinson J. An essay on the shaking palsy. 1817. J Neuropsychiatry Clin Neurosci  2002; 14(2): 223-36.
[http://dx.doi.org/10.1176/jnp.14.2.223] [PMID: 11983801] 
[44] 
Kalia LV, Lang AE. Parkinson’s disease. Lancet  2015; 386(9996): 896-912.
[http://dx.doi.org/10.1016/S0140-6736(14)61393-3] [PMID: 25904081] 
[45] 
Twelves D, Perkins KS, Counsell C. Systematic review of incidence studies of Parkinson’s disease. Mov Disord  2003; 18(1): 19-31.
[http://dx.doi.org/10.1002/mds.10305] [PMID: 12518297] 
[46] 
Savica R, Grossardt BR, Bower JH, Ahlskog JE, Rocca WA. Incidence and pathology of synucleinopathies and tauopathies related to parkinsonism. JAMA Neurol  2013; 70(7): 859-66.
[http://dx.doi.org/10.1001/jamaneurol.2013.114] [PMID: 23689920] 
[47] 
Van Den Eeden SK, Tanner CM, Bernstein AL, et al. Incidence of Parkinson’s disease: variation by age, gender, and race/ethnicity. Am J Epidemiol  2003; 157(11): 1015-22.
[http://dx.doi.org/10.1093/aje/kwg068] [PMID: 12777365] 
[48] 
Dorsey ER, Constantinescu R, Thompson JP, et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology  2007; 68(5): 384-6.
[http://dx.doi.org/10.1212/01.wnl.0000247740.47667.03] [PMID: 17082464] 
[49] 
Baldereschi M, Di Carlo A, Rocca WA, et al. ILSA Working Group. Italian Longitudinal Study on Aging. Parkinson’s disease and parkinsonism in a longitudinal study: two-fold higher incidence in men. Neurology  2000; 55(9): 1358-63.
[http://dx.doi.org/10.1212/WNL.55.9.1358] [PMID: 11087781] 
[50] 
Ascherio A, Schwarzschild MA. The epidemiology of Parkinson’s disease: risk factors and prevention. Lancet Neurol  2016; 15(12): 1257-72.
[http://dx.doi.org/10.1016/S1474-4422(16)30230-7] [PMID: 27751556] 
[51] 
Gibb WR, Lees AJ. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry  1988; 51(6): 745-52.
[http://dx.doi.org/10.1136/jnnp.51.6.745] [PMID: 2841426] 
[52] 
Jankovic J, McDermott M, Carter J, et al. The Parkinson Study Group. Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. Neurology  1990; 40(10): 1529-34.
[http://dx.doi.org/10.1212/WNL.40.10.1529] [PMID: 2215943] 
[53] 
Marras C, Lang A. Parkinson’s disease subtypes: lost in translation? J Neurol Neurosurg Psychiatry  2013; 84(4): 409-15.
[http://dx.doi.org/10.1136/jnnp-2012-303455] [PMID: 22952329] 
[54] 
Khoo TK, Yarnall AJ, Duncan GW, et al. The spectrum of nonmotor symptoms in early Parkinson disease. Neurology  2013; 80(3): 276-81.
[http://dx.doi.org/10.1212/WNL.0b013e31827deb74] [PMID: 23319473] 
[55] 
Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers  2017; 3: 17013.
[http://dx.doi.org/10.1038/nrdp.2017.13] [PMID: 28332488] 
[56] 
Dickson DW, Braak H, Duda JE, et al. Neuropathological assessment of Parkinson’s disease: refining the diagnostic criteria. Lancet Neurol  2009; 8(12): 1150-7.
[http://dx.doi.org/10.1016/S1474-4422(09)70238-8] [PMID: 19909913] 
[57] 
Halliday GM, Holton JL, Revesz T, Dickson DW. Neuropathology underlying clinical variability in patients with synucleinopathies. Acta Neuropathol  2011; 122(2): 187-204.
[http://dx.doi.org/10.1007/s00401-011-0852-9] [PMID: 21720849] 
[58] 
Damier P, Hirsch EC, Agid Y, Graybiel AM. The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson’s disease. Brain  1999; 122(Pt 8): 1437-48.
[http://dx.doi.org/10.1093/brain/122.8.1437] [PMID: 10430830] 
[59] 
Fearnley JM, Lees AJ. Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain  1991; 114(Pt 5): 2283-301.
[http://dx.doi.org/10.1093/brain/114.5.2283] [PMID: 1933245] 
[60] 
Iacono D, Geraci-Erck M, Rabin ML, et al. Parkinson disease and incidental Lewy body disease: Just a question of time? Neurology  2015; 85(19): 1670-9.
[http://dx.doi.org/10.1212/WNL.0000000000002102] [PMID: 26468408] 
[61] 
Nalls MA, Pankratz N, Lill CM, et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nat Genet  2014; 46(9): 989-93.
[http://dx.doi.org/10.1038/ng.3043] [PMID: 25064009] 
[62] 
Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord  2015; 30(12): 1591-601.
[http://dx.doi.org/10.1002/mds.26424] [PMID: 26474316] 
[63] 
Tolosa E, Wenning G, Poewe W. The diagnosis of Parkinson’s disease. Lancet Neurol  2006; 5(1): 75-86.
[http://dx.doi.org/10.1016/S1474-4422(05)70285-4] [PMID: 16361025] 
[64] 
Alcalay RN, Caccappolo E, Mejia-Santana H, et al. Frequency of known mutations in early-onset Parkinson disease: implication for genetic counseling: the consortium on risk for early onset Parkinson disease study. Arch Neurol  2010; 67(9): 1116-22.
[http://dx.doi.org/10.1001/archneurol.2010.194] [PMID: 20837857] 
[65] 
Marder KS, Tang MX, Mejia-Santana H, et al. Predictors of parkin mutations in early-onset Parkinson disease: the consortium on risk for early-onset Parkinson disease study. Arch Neurol  2010; 67(6): 731-8.
[http://dx.doi.org/10.1001/archneurol.2010.95] [PMID: 20558392] 
[66] 
Garnett ES, Firnau G, Nahmias C. Dopamine visualized in the basal ganglia of living man. Nature  1983; 305(5930): 137-8.
[http://dx.doi.org/10.1038/305137a0] [PMID: 6604227] 
[67] 
Mahlknecht P, Hotter A, Hussl A, Esterhammer R, Schocke M, Seppi K. Significance of MRI in diagnosis and differential diagnosis of Parkinson’s disease. Neurodegener Dis  2010; 7(5): 300-18.
[http://dx.doi.org/10.1159/000314495] [PMID: 20616565] 
[68] 
Politis M. Neuroimaging in Parkinson disease: from research setting to clinical practice. Nat Rev Neurol  2014; 10(12): 708-22.
[http://dx.doi.org/10.1038/nrneurol.2014.205] [PMID: 25385334] 
[69] 
Stoessl AJ, Lehericy S, Strafella AP. Imaging insights into basal ganglia function, Parkinson’s disease, and dystonia. Lancet  2014; 384(9942): 532-44.
[http://dx.doi.org/10.1016/S0140-6736(14)60041-6] [PMID: 24954673] 
[70] 
Lill CM. Genetics of Parkinson’s disease. Mol Cell Probes  2016; 30(6): 386-96.
[http://dx.doi.org/10.1016/j.mcp.2016.11.001] [PMID: 27818248] 
[71] 
Marras C, Lang A, van de Warrenburg BP, et al. Nomenclature of genetic movement disorders: Recommendations of the international Parkinson and movement disorder society task force. Mov Disord  2016; 31(4): 436-57.
[http://dx.doi.org/10.1002/mds.26527] [PMID: 27079681] 
[72] 
Gray R, Ives N, Rick C, et al. PD Med Collaborative Group. Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson’s disease (PD MED): a large, open-label, pragmatic randomised trial. Lancet  2014; 384(9949): 1196-205.
[http://dx.doi.org/10.1016/S0140-6736(14)60683-8] [PMID: 24928805] 
[73] 
LeWitt PA, Fahn S. Levodopa therapy for Parkinson disease: A look backward and forward. Neurology  2016; 86(14)(Suppl. 1): S3-S12.
[http://dx.doi.org/10.1212/WNL.0000000000002509] [PMID: 27044648] 
[74] 
Müller T. Catechol-O-methyltransferase inhibitors in Parkinson’s disease. Drugs  2015; 75(2): 157-74.
[http://dx.doi.org/10.1007/s40265-014-0343-0] [PMID: 25559423] 
[75] 
Birkmayer W, Riederer P, Ambrozi L, Youdim MB. Implications of combined treatment with ‘Madopar’ and L-deprenil in Parkinson’s disease. A long-term study. Lancet  1977; 1(8009): 439-43.
[http://dx.doi.org/10.1016/S0140-6736(77)91940-7] [PMID: 65560] 
[76] 
Fox SH, Katzenschlager R, Lim SY, et al. The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the motor symptoms of Parkinson’s disease. Mov Disord  2011; 26(Suppl. 3): S2-S41.
[http://dx.doi.org/10.1002/mds.23829] [PMID: 22021173] 
[77] 
Schapira AH, Fox SH, Hauser RA, et al. Assessment of Safety and Efficacy of Safinamide as a Levodopa Adjunct in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. JAMA Neurol  2017; 74(2): 216-24.
[http://dx.doi.org/10.1001/jamaneurol.2016.4467] [PMID: 27942720] 
[78] 
Karran E, Mercken M, De Strooper B. The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov  2011; 10(9): 698-712.
[http://dx.doi.org/10.1038/nrd3505] [PMID: 21852788] 
[79] 
Boyle PA, Wilson RS, Yu L, et al. Much of late life cognitive decline is not due to common neurodegenerative pathologies. Ann Neurol  2013; 74(3): 478-89.
[http://dx.doi.org/10.1002/ana.23964] [PMID: 23798485] 
[80] 
Cummings JL, Doody R, Clark C. Disease-modifying therapies for Alzheimer disease: challenges to early intervention. Neurology  2007; 69(16): 1622-34.
[http://dx.doi.org/10.1212/01.wnl.0000295996.54210.69] [PMID: 17938373] 
[81] 
Deane R, Bell RD, Sagare A, Zlokovic BV. Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer’s disease. CNS Neurol Disord Drug Targets  2009; 8(1): 16-30.
[http://dx.doi.org/10.2174/187152709787601867] [PMID: 19275634] 
[82] 
Mohandas E, Rajmohan V, Raghunath B. Neurobiology of Alzheimer’s disease. Indian J Psychiatry  2009; 51(1): 55-61.
[http://dx.doi.org/10.4103/0019-5545.44908] [PMID: 19742193] 
[83] 
Bertram L, Tanzi RE. Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci  2008; 9(10): 768-78.
[http://dx.doi.org/10.1038/nrn2494] [PMID: 18802446] 
[84] 
McGowan E, Pickford F, Kim J, et al. Abeta42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron  2005; 47(2): 191-9.
[http://dx.doi.org/10.1016/j.neuron.2005.06.030] [PMID: 16039562] 
[85] 
Goedert M, Spillantini MG. A century of Alzheimer’s disease. Science  2006; 314(5800): 777-81.
[http://dx.doi.org/10.1126/science.1132814] [PMID: 17082447] 
[86] 
Wang DS, Dickson DW, Malter JS. beta-Amyloid degradation and Alzheimer’s disease. J Biomed Biotechnol  2006; 2006(3): 58406.
[PMID: 17047308] 
[87] 
Chen X, Walker DG, Schmidt AM, Arancio O, Lue LF, Yan SD. RAGE: a potential target for Abeta-mediated cellular perturbation in Alzheimer’s disease. Curr Mol Med  2007; 7(8): 735-42.
[http://dx.doi.org/10.2174/156652407783220741] [PMID: 18331231] 
[88] 
Miners JS, Baig S, Tayler H, Kehoe PG, Love S. Neprilysin and insulin-degrading enzyme levels are increased in Alzheimer disease in relation to disease severity. J Neuropathol Exp Neurol  2009; 68(8): 902-14.
[http://dx.doi.org/10.1097/NEN.0b013e3181afe475] [PMID: 19606063] 
[89] 
Pasternak SH, Callahan JW, Mahuran DJ. The role of the endosomal/lysosomal system in amyloid-beta production and the pathophysiology of Alzheimer’s disease: reexamining the spatial paradox from a lysosomal perspective. J Alzheimers Dis  2004; 6(1): 53-65.
[http://dx.doi.org/10.3233/JAD-2004-6107] [PMID: 15004328] 
[90] 
Boland B, Kumar A, Lee S, et al. Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease. J Neurosci  2008; 28(27): 6926-37.
[http://dx.doi.org/10.1523/JNEUROSCI.0800-08.2008] [PMID: 18596167] 
[91] 
Hara T, Nakamura K, Matsui M, et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature  2006; 441(7095): 885-9.
[http://dx.doi.org/10.1038/nature04724] [PMID: 16625204] 
[92] 
Komatsu M, Waguri S, Chiba T, et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature  2006; 441(7095): 880-4.
[http://dx.doi.org/10.1038/nature04723] [PMID: 16625205] 
[93] 
Simón AM, Frechilla D, del Río J. [Perspectives on the amyloid cascade hypothesis of Alzheimer’s disease]. Rev Neurol  2010; 50(11): 667-75. [Perspectives on the amyloid cascade hypothesis of Alzheimer's disease].
[PMID: 20514639] 
[94] 
Roberson ED, Scearce-Levie K, Palop JJ, et al. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model. Science  2007; 316(5825): 750-4.
[http://dx.doi.org/10.1126/science.1141736] [PMID: 17478722] 
[95] 
Goedert M, Klug A, Crowther RA. Tau protein, the paired helical filament and Alzheimer’s disease. J Alzheimers Dis  2006; 9(3)(Suppl.): 195-207.
[http://dx.doi.org/10.3233/JAD-2006-9S323] [PMID: 16914859] 
[96] 
Kuret J, Congdon EE, Li G, Yin H, Yu X, Zhong Q. Evaluating triggers and enhancers of tau fibrillization. Microsc Res Tech  2005; 67(3-4): 141-55.
[http://dx.doi.org/10.1002/jemt.20187] [PMID: 16103995] 
[97] 
Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature  2006; 443(7113): 787-95.
[http://dx.doi.org/10.1038/nature05292] [PMID: 17051205] 
[98] 
Gandhi S, Abramov AY. Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev  2012; 2012: 428010.
[http://dx.doi.org/10.1155/2012/428010] [PMID: 22685618] 
[99] 
Praticò D. Oxidative stress hypothesis in Alzheimer’s disease: a reappraisal. Trends Pharmacol Sci  2008; 29(12): 609-15.
[http://dx.doi.org/10.1016/j.tips.2008.09.001] [PMID: 18838179] 
[100] 
Makhaeva GF, Lushchekina SV, Boltneva NP, et al. Conjugates of γ-Carbolines and Phenothiazine as new selective inhibitors of butyrylcholinesterase and blockers of NMDA receptors for Alzheimer Disease. Sci Rep  2015; 5: 13164.
[http://dx.doi.org/10.1038/srep13164] [PMID: 26281952] 
[101] 
Zhao Y, Zhao B. Oxidative stress and the pathogenesis of Alzheimer’s disease. Oxid Med Cell Longev  2013; 2013: 316523.
[http://dx.doi.org/10.1155/2013/316523] [PMID: 23983897] 
[102] 
Hirai K, Aliev G, Nunomura A, et al. Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci  2001; 21(9): 3017-23.
[http://dx.doi.org/10.1523/JNEUROSCI.21-09-03017.2001] [PMID: 11312286] 
[103] 
Zhu X, Perry G, Moreira PI, et al. Mitochondrial abnormalities and oxidative imbalance in Alzheimer disease. J Alzheimers Dis  2006; 9(2): 147-53.
[http://dx.doi.org/10.3233/JAD-2006-9207] [PMID: 16873962] 
[104] 
Magi S, Castaldo P, Macrì ML, et al. Intracellular Calcium Dysregulation: Implications for Alzheimer’s Disease. BioMed Res Int  2016; 2016: 6701324.
[http://dx.doi.org/10.1155/2016/6701324] [PMID: 27340665] 
[105] 
Small DH. Dysregulation of calcium homeostasis in Alzheimer’s disease. Neurochem Res  2009; 34(10): 1824-9.
[http://dx.doi.org/10.1007/s11064-009-9960-5] [PMID: 19337829] 
[106] 
Wang JM, Sun C. Calcium and neurogenesis in Alzheimer’s disease. Front Neurosci  2010; 4: 194.
[http://dx.doi.org/10.3389/fnins.2010.00194] [PMID: 21151820] 
[107] 
Arispe N, Rojas E, Pollard HB. Alzheimer disease amyloid beta protein forms calcium channels in bilayer membranes: blockade by tromethamine and aluminum. Proc Natl Acad Sci USA  1993; 90(2): 567-71.
[http://dx.doi.org/10.1073/pnas.90.2.567] [PMID: 8380642] 
[108] 
Schaeffer EL, Gattaz WF. Cholinergic and glutamatergic alterations beginning at the early stages of Alzheimer disease: participation of the phospholipase A2 enzyme. Psychopharmacology (Berl)  2008; 198(1): 1-27.
[http://dx.doi.org/10.1007/s00213-008-1092-0] [PMID: 18392810] 
[109] 
Mesulam M. The cholinergic lesion of Alzheimer’s disease: pivotal factor or side show? Learn Mem  2004; 11(1): 43-9.
[http://dx.doi.org/10.1101/lm.69204] [PMID: 14747516] 
[110] 
Ni R, Marutle A, Nordberg A. Modulation of α7 nicotinic acetylcholine receptor and fibrillar amyloid-β interactions in Alzheimer’s disease brain. J Alzheimers Dis  2013; 33(3): 841-51.
[http://dx.doi.org/10.3233/JAD-2012-121447] [PMID: 23042213] 
[111] 
Shen J, Wu J. Nicotinic Cholinergic Mechanisms in Alzheimer's Disease. Int Rev Neurobiol  2015; 124: 275-92.
[112] 
Dong XX, Wang Y, Qin ZH. Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases. Acta Pharmacol Sin  2009; 30(4): 379-87.
[http://dx.doi.org/10.1038/aps.2009.24] [PMID: 19343058] 
[113] 
Doggrell SA, Evans S. Treatment of dementia with neurotransmission modulation. Expert Opin Investig Drugs  2003; 12(10): 1633-54.
[http://dx.doi.org/10.1517/13543784.12.10.1633] [PMID: 14519085] 
[114] 
Olsen I, Singhrao SK. Inflammasome Involvement in Alzheimer’s Disease. J Alzheimers Dis  2016; 54(1): 45-53.
[http://dx.doi.org/10.3233/JAD-160197] [PMID: 27314526] 
[115] 
Itzhaki RF, Lathe R, Balin BJ, et al. Microbes and Alzheimer’s Disease. J Alzheimers Dis  2016; 51(4): 979-84.
[http://dx.doi.org/10.3233/JAD-160152] [PMID: 26967229] 
[116] 
Miklossy J. Historic evidence to support a causal relationship between spirochetal infections and Alzheimer’s disease. Front Aging Neurosci  2015; 7: 46.
[http://dx.doi.org/10.3389/fnagi.2015.00046] [PMID: 25932012] 
[117] 
Gasque P. Complement: a unique innate immune sensor for danger signals. Mol Immunol  2004; 41(11): 1089-98.
[http://dx.doi.org/10.1016/j.molimm.2004.06.011] [PMID: 15476920] 
[118] 
Salminen A, Ojala J, Suuronen T, Kaarniranta K, Kauppinen A. Amyloid-beta oligomers set fire to inflammasomes and induce Alzheimer’s pathology. J Cell Mol Med  2008; 12(6A): 2255-62.
[http://dx.doi.org/10.1111/j.1582-4934.2008.00496.x] [PMID: 18793350] 
[119] 
Heneka MT, Kummer MP, Stutz A, et al. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature  2013; 493(7434): 674-8.
[http://dx.doi.org/10.1038/nature11729] [PMID: 23254930] 
[120] 
Qazi O, Parthasarathy PT, Lockey R, Kolliputi N. Can microRNAs keep inflammasomes in check? Front Genet  2013; 4: 30.
[http://dx.doi.org/10.3389/fgene.2013.00030] [PMID: 23495355] 
[121] 
Tan MS, Yu JT, Jiang T, Zhu XC, Tan L. The NLRP3 inflammasome in Alzheimer’s disease. Mol Neurobiol  2013; 48(3): 875-82.
[http://dx.doi.org/10.1007/s12035-013-8475-x] [PMID: 23686772] 
[122] 
Xiong Z, Thangavel R, Kempuraj D, Yang E, Zaheer S, Zaheer A. Alzheimer’s disease: evidence for the expression of interleukin-33 and its receptor ST2 in the brain. J Alzheimers Dis  2014; 40(2): 297-308.
[http://dx.doi.org/10.3233/JAD-132081] [PMID: 24413615] 
[123] 
Saco T, Parthasarathy PT, Cho Y, Lockey RF, Kolliputi N. Inflammasome: a new trigger of Alzheimer’s disease. Front Aging Neurosci  2014; 6: 80.
[http://dx.doi.org/10.3389/fnagi.2014.00080] [PMID: 24834051] 
[124] 
Walsh JG, Muruve DA, Power C. Inflammasomes in the CNS. Nat Rev Neurosci  2014; 15(2): 84-97.
[http://dx.doi.org/10.1038/nrn3638] [PMID: 24399084] 
[125] 
Abais JM, Xia M, Zhang Y, Boini KM, Li PL. Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector? Antioxid Redox Signal  2015; 22(13): 1111-29.
[http://dx.doi.org/10.1089/ars.2014.5994] [PMID: 25330206] 
[126] 
Singhal G, Jaehne EJ, Corrigan F, Toben C, Baune BT. Inflammasomes in neuroinflammation and changes in brain function: a focused review. Front Neurosci  2014; 8: 315.
[http://dx.doi.org/10.3389/fnins.2014.00315] [PMID: 25339862] 
[127] 
Weber A, Wasiliew P, Kracht M. Interleukin-1beta (IL-1beta) processing pathway. Sci Signal  2010; 3(105): cm2.
[PMID: 20086236] 
[128] 
Blum-Degen D, Müller T, Kuhn W, Gerlach M, Przuntek H, Riederer P. Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer’s and de novo Parkinson’s disease patients. Neurosci Lett  1995; 202(1-2): 17-20.
[http://dx.doi.org/10.1016/0304-3940(95)12192-7] [PMID: 8787820] 
[129] 
Cacabelos R, Franco-Maside A, Alvarez XA. Interleukin-1 in Alzheimer’s disease and multi-infarct dementia: neuropsychological correlations. Methods Find Exp Clin Pharmacol  1991; 13(10): 703-8.
[PMID: 1770834] 
[130] 
Déniz-Naranjo MC, Muñoz-Fernandez C, Alemany-Rodríguez MJ, et al. Cytokine IL-1 beta but not IL-1 alpha promoter polymorphism is associated with Alzheimer disease in a population from the Canary Islands, Spain. Eur J Neurol  2008; 15(10): 1080-4.
[http://dx.doi.org/10.1111/j.1468-1331.2008.02252.x] [PMID: 18717723] 
[131] 
Malaguarnera L, Motta M, Di Rosa M, Anzaldi M, Malaguarnera M. Interleukin-18 and transforming growth factor-beta 1 plasma levels in Alzheimer’s disease and vascular dementia. Neuropathology  2006; 26(4): 307-12.
[http://dx.doi.org/10.1111/j.1440-1789.2006.00701.x] [PMID: 16961066] 
[132] 
Oztürk C, Ozge A, Yalin OO, et al. The diagnostic role of serum inflammatory and soluble proteins on dementia subtypes: correlation with cognitive and functional decline. Behav Neurol  2007; 18(4): 207-15.
[http://dx.doi.org/10.1155/2007/432190] [PMID: 18430978] 
[133] 
Sutinen EM, Pirttilä T, Anderson G, Salminen A, Ojala JO. Pro-inflammatory interleukin-18 increases Alzheimer’s disease-associated amyloid-β production in human neuron-like cells. J Neuroinflammation  2012; 9: 199.
[http://dx.doi.org/10.1186/1742-2094-9-199] [PMID: 22898493] 
[134] 
Rathinam VA, Vanaja SK, Fitzgerald KA. Regulation of inflammasome signaling. Nat Immunol  2012; 13(4): 333-42.
[http://dx.doi.org/10.1038/ni.2237] [PMID: 22430786] 
[135] 
Balin BJ, Little CS, Hammond CJ, et al. Chlamydophila pneumoniae and the etiology of late-onset Alzheimer’s disease. J Alzheimers Dis  2008; 13(4): 371-80.
[http://dx.doi.org/10.3233/JAD-2008-13403] [PMID: 18487846] 
[136] 
MacDonald AB, Miranda JM. Concurrent neocortical borreliosis and Alzheimer’s disease. Hum Pathol  1987; 18(7): 759-61.
[http://dx.doi.org/10.1016/S0046-8177(87)80252-6] [PMID: 3297997] 
[137] 
Miklossy J. Alzheimer’s disease--a spirochetosis? Neuroreport  1993; 4(7): 841-8.
[http://dx.doi.org/10.1097/00001756-199307000-00002] [PMID: 8369471] 
[138] 
Miklossy J. Alzheimer’s disease - a neurospirochetosis. Analysis of the evidence following Koch’s and Hill’s criteria. J Neuroinflammation  2011; 8: 90.
[http://dx.doi.org/10.1186/1742-2094-8-90] [PMID: 21816039] 
[139] 
von Moltke J, Ayres JS, Kofoed EM, Chavarría-Smith J, Vance RE. Recognition of bacteria by inflammasomes. Annu Rev Immunol  2013; 31: 73-106.
[http://dx.doi.org/10.1146/annurev-immunol-032712-095944] [PMID: 23215645] 
[140] 
Karch CM, Goate AM. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry  2015; 77(1): 43-51.
[http://dx.doi.org/10.1016/j.biopsych.2014.05.006] [PMID: 24951455] 
[141] 
Cacace R, Sleegers K, Van Broeckhoven C. Molecular genetics of early-onset Alzheimer’s disease revisited. Alzheimers Dement  2016; 12(6): 733-48.
[http://dx.doi.org/10.1016/j.jalz.2016.01.012] [PMID: 27016693] 
[142] 
Morris JC, Roe CM, Xiong C, et al. APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol  2010; 67(1): 122-31.
[http://dx.doi.org/10.1002/ana.21843] [PMID: 20186853] 
[143] 
Shi Y, Yamada K, Liddelow SA, et al. Alzheimer’s Disease Neuroimaging Initiative. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature  2017; 549(7673): 523-7.
[http://dx.doi.org/10.1038/nature24016] [PMID: 28959956] 
[144] 
Spira AP, Gamaldo AA, An Y, et al. Self-reported sleep and β-amyloid deposition in community-dwelling older adults. JAMA Neurol  2013; 70(12): 1537-43.
[http://dx.doi.org/10.1001/jamaneurol.2013.4258] [PMID: 24145859] 
[145] 
Sprecher KE, Bendlin BB, Racine AM, et al. Amyloid burden is associated with self-reported sleep in nondemented late middle-aged adults. Neurobiol Aging  2015; 36(9): 2568-76.
[http://dx.doi.org/10.1016/j.neurobiolaging.2015.05.004] [PMID: 26059712] 
[146] 
Landau SM, Marks SM, Mormino EC, et al. Association of lifetime cognitive engagement and low β-amyloid deposition. Arch Neurol  2012; 69(5): 623-9.
[http://dx.doi.org/10.1001/archneurol.2011.2748] [PMID: 22271235] 
[147] 
Vemuri P, Lesnick TG, Przybelski SA, et al. Effect of intellectual enrichment on AD biomarker trajectories: Longitudinal imaging study. Neurology  2016; 86(12): 1128-35.
[http://dx.doi.org/10.1212/WNL.0000000000002490] [PMID: 26911640] 
[148] 
Cicero CE, Mostile G, Vasta R, et al. Metals and neurodegenerative diseases. A systematic review. Environ Res  2017; 159: 82-94.
[http://dx.doi.org/10.1016/j.envres.2017.07.048] [PMID: 28777965] 
[149] 
Yan D, Zhang Y, Liu L, Yan H. Pesticide exposure and risk of Alzheimer’s disease: a systematic review and meta-analysis. Sci Rep  2016; 6: 32222.
[http://dx.doi.org/10.1038/srep32222] [PMID: 27581992] 
[150] 
Vekrellis K, Xilouri M, Emmanouilidou E, Rideout HJ, Stefanis L. Pathological roles of α-synuclein in neurological disorders. Lancet Neurol  2011; 10(11): 1015-25.
[http://dx.doi.org/10.1016/S1474-4422(11)70213-7] [PMID: 22014436] 
[151] 
Burré J. The Synaptic Function of α-Synuclein. J Parkinsons Dis  2015; 5(4): 699-713.
[http://dx.doi.org/10.3233/JPD-150642] [PMID: 26407041] 
[152] 
Wales P, Pinho R, Lázaro DF, Outeiro TF. Limelight on alpha-synuclein: pathological and mechanistic implications in neurodegeneration. J Parkinsons Dis  2013; 3(4): 415-59.
[http://dx.doi.org/10.3233/JPD-130216] [PMID: 24270242] 
[153] 
Kim C, Lee SJ. Controlling the mass action of alpha-synuclein in Parkinson’s disease. J Neurochem  2008; 107(2): 303-16.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05612.x] [PMID: 18691382] 
[154] 
Melki R. Role of Different Alpha-Synuclein Strains in Synucleinopathies, Similarities with other Neurodegenerative Diseases. J Parkinsons Dis  2015; 5(2): 217-27.
[http://dx.doi.org/10.3233/JPD-150543] [PMID: 25757830] 
[155] 
Kaushik S, Cuervo AM. Proteostasis and aging. Nat Med  2015; 21(12): 1406-15.
[http://dx.doi.org/10.1038/nm.4001] [PMID: 26646497] 
[156] 
Xilouri M, Brekk OR, Stefanis L. α-Synuclein and protein degradation systems: a reciprocal relationship. Mol Neurobiol  2013; 47(2): 537-51.
[http://dx.doi.org/10.1007/s12035-012-8341-2] [PMID: 22941029] 
[157] 
Chu Y, Kordower JH. Age-associated increases of alpha-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: Is this the target for Parkinson’s disease? Neurobiol Dis  2007; 25(1): 134-49.
[http://dx.doi.org/10.1016/j.nbd.2006.08.021] [PMID: 17055279] 
[158] 
Alvarez-Erviti L, Rodriguez-Oroz MC, Cooper JM, et al. Chaperone-mediated autophagy markers in Parkinson disease brains. Arch Neurol  2010; 67(12): 1464-72.
[http://dx.doi.org/10.1001/archneurol.2010.198] [PMID: 20697033] 
[159] 
Anglade P, Vyas S, Javoy-Agid F, et al. Apoptosis and autophagy in nigral neurons of patients with Parkinson’s disease. Histol Histopathol  1997; 12(1): 25-31.
[PMID: 9046040] 
[160] 
Chu Y, Dodiya H, Aebischer P, Olanow CW, Kordower JH. Alterations in lysosomal and proteasomal markers in Parkinson’s disease: relationship to alpha-synuclein inclusions. Neurobiol Dis  2009; 35(3): 385-98.
[http://dx.doi.org/10.1016/j.nbd.2009.05.023] [PMID: 19505575] 
[161] 
Sarkar S, Davies JE, Huang Z, Tunnacliffe A, Rubinsztein DC. Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein. J Biol Chem  2007; 282(8): 5641-52.
[http://dx.doi.org/10.1074/jbc.M609532200] [PMID: 17182613] 
[162] 
Steele JW, Ju S, Lachenmayer ML, et al. Latrepirdine stimulates autophagy and reduces accumulation of α-synuclein in cells and in mouse brain. Mol Psychiatry  2013; 18(8): 882-8.
[http://dx.doi.org/10.1038/mp.2012.115] [PMID: 22869031] 
[163] 
Emmanouilidou E, Stefanis L, Vekrellis K. Cell-produced alpha-synuclein oligomers are targeted to, and impair, the 26S proteasome. Neurobiol Aging  2010; 31(6): 953-68.
[http://dx.doi.org/10.1016/j.neurobiolaging.2008.07.008] [PMID: 18715677] 
[164] 
Tanik SA, Schultheiss CE, Volpicelli-Daley LA, Brunden KR, Lee VM. Lewy body-like α-synuclein aggregates resist degradation and impair macroautophagy. J Biol Chem  2013; 288(21): 15194-210.
[http://dx.doi.org/10.1074/jbc.M113.457408] [PMID: 23532841] 
[165] 
Winslow AR, Chen CW, Corrochano S, et al. α-Synuclein impairs macroautophagy: implications for Parkinson’s disease. J Cell Biol  2010; 190(6): 1023-37.
[http://dx.doi.org/10.1083/jcb.201003122] [PMID: 20855506] 
[166] 
Fernandes HJ, Hartfield EM, Christian HC, et al. ER Stress and Autophagic Perturbations Lead to Elevated Extracellular α-Synuclein in GBA-N370S Parkinson’s iPSC-Derived Dopamine Neurons. Stem Cell Reports  2016; 6(3): 342-56.
[http://dx.doi.org/10.1016/j.stemcr.2016.01.013] [PMID: 26905200] 
[167] 
Sidransky E, Nalls MA, Aasly JO, et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease. N Engl J Med  2009; 361(17): 1651-61.
[http://dx.doi.org/10.1056/NEJMoa0901281] [PMID: 19846850] 
[168] 
Volpicelli-Daley LA, Abdelmotilib H, Liu Z, et al. G2019S-LRRK2 Expression Augments α-Synuclein Sequestration into Inclusions in Neurons. J Neurosci  2016; 36(28): 7415-27.
[http://dx.doi.org/10.1523/JNEUROSCI.3642-15.2016] [PMID: 27413152] 
[169] 
Tang FL, Erion JR, Tian Y, et al. VPS35 in Dopamine Neurons Is Required for Endosome-to-Golgi Retrieval of Lamp2a, a Receptor of Chaperone-Mediated Autophagy That Is Critical for α-Synuclein Degradation and Prevention of Pathogenesis of Parkinson’s Disease. J Neurosci  2015; 35(29): 10613-28.
[http://dx.doi.org/10.1523/JNEUROSCI.0042-15.2015] [PMID: 26203154] 
[170] 
Vilariño-Güell C, Wider C, Ross OA, et al. VPS35 mutations in Parkinson disease. Am J Hum Genet  2011; 89(1): 162-7.
[http://dx.doi.org/10.1016/j.ajhg.2011.06.001] [PMID: 21763482] 
[171] 
Zimprich A, Benet-Pagès A, Struhal W, et al. A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. Am J Hum Genet  2011; 89(1): 168-75.
[http://dx.doi.org/10.1016/j.ajhg.2011.06.008] [PMID: 21763483] 
[172] 
Angot E, Steiner JA, Hansen C, Li JY, Brundin P. Are synucleinopathies prion-like disorders? Lancet Neurol  2010; 9(11): 1128-38.
[http://dx.doi.org/10.1016/S1474-4422(10)70213-1] [PMID: 20846907] 
[173] 
Brundin P, Melki R, Kopito R. Prion-like transmission of protein aggregates in neurodegenerative diseases. Nat Rev Mol Cell Biol  2010; 11(4): 301-7.
[http://dx.doi.org/10.1038/nrm2873] [PMID: 20308987] 
[174] 
Mao X, Ou MT, Karuppagounder SS, et al. Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3. Science  2016; 353(6307): 353.
[http://dx.doi.org/10.1126/science.aah3374] [PMID: 27708076] 
[175] 
Tyson T, Steiner JA, Brundin P. Sorting out release, uptake and processing of alpha-synuclein during prion-like spread of pathology. J Neurochem  2016; 139(Suppl. 1): 275-89.
[http://dx.doi.org/10.1111/jnc.13449] [PMID: 26617280] 
[176] 
Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging  2003; 24(2): 197-211.
[http://dx.doi.org/10.1016/S0197-4580(02)00065-9] [PMID: 12498954] 
[177] 
Chaturvedi RK, Beal MF. Mitochondrial approaches for neuroprotection. Ann N Y Acad Sci  2008; 1147: 395-412.
[http://dx.doi.org/10.1196/annals.1427.027] [PMID: 19076459] 
[178] 
Chaturvedi RK, Beal MF. PPAR: a therapeutic target in Parkinson’s disease. J Neurochem  2008; 106(2): 506-18.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05388.x] [PMID: 18384649] 
[179] 
Bose A, Beal MF. Mitochondrial dysfunction in Parkinson’s disease. J Neurochem  2016; 139(Suppl. 1): 216-31.
[http://dx.doi.org/10.1111/jnc.13731] [PMID: 27546335] 
[180] 
Devi L, Raghavendran V, Prabhu BM, Avadhani NG, Anandatheerthavarada HK. Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. J Biol Chem  2008; 283(14): 9089-100.
[http://dx.doi.org/10.1074/jbc.M710012200] [PMID: 18245082] 
[181] 
Schapira AH. Mitochondrial dysfunction in Parkinson’s disease. Cell Death Differ  2007; 14(7): 1261-6.
[http://dx.doi.org/10.1038/sj.cdd.4402160] [PMID: 17464321] 
[182] 
Agarwal S, Yadav A, Chaturvedi RK. Peroxisome proliferator-activated receptors (PPARs) as therapeutic target in neurodegenerative disorders. Biochem Biophys Res Commun  2017; 483(4): 1166-77.
[http://dx.doi.org/10.1016/j.bbrc.2016.08.043] [PMID: 27514452] 
[183] 
Chaturvedi RK, Beal MF. Mitochondria targeted therapeutic approaches in Parkinson’s and Huntington’s diseases. Mol Cell Neurosci  2013; 55: 101-14.
[http://dx.doi.org/10.1016/j.mcn.2012.11.011] [PMID: 23220289] 
[184] 
Chaturvedi RK, Flint Beal M. Mitochondrial diseases of the brain. Free Radic Biol Med  2013; 63: 1-29.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.03.018] [PMID: 23567191] 
[185] 
Yadav A, Agarwal S, Tiwari SK, Chaturvedi RK. Mitochondria: prospective targets for neuroprotection in Parkinson’s disease. Curr Pharm Des  2014; 20(35): 5558-73.
[http://dx.doi.org/10.2174/1381612820666140305224545] [PMID: 24606805] 
[186] 
Eschbach J, von Einem B, Müller K, et al. Mutual exacerbation of peroxisome proliferator-activated receptor γ coactivator 1α deregulation and α-synuclein oligomerization. Ann Neurol  2015; 77(1): 15-32.
[http://dx.doi.org/10.1002/ana.24294] [PMID: 25363075] 
[187] 
Zheng B, Liao Z, Locascio JJ, et al. Global PD Gene Expression (GPEX) Consortium. PGC-1α, a potential therapeutic target for early intervention in Parkinson’s disease. Sci Transl Med  2010; 2(52): 52ra73.
[http://dx.doi.org/10.1126/scitranslmed.3001059] [PMID: 20926834] 
[188] 
Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron  2015; 85(2): 257-73.
[http://dx.doi.org/10.1016/j.neuron.2014.12.007] [PMID: 25611507] 
[189] 
Bonifati V, Rizzu P, van Baren MJ, et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science  2003; 299(5604): 256-9.
[http://dx.doi.org/10.1126/science.1077209] [PMID: 12446870] 
[190] 
Di Nottia M, Masciullo M, Verrigni D, et al. DJ-1 modulates mitochondrial response to oxidative stress: clues from a novel diagnosis of PARK7. Clin Genet  2017; 92(1): 18-25.
[http://dx.doi.org/10.1111/cge.12841] [PMID: 27460976] 
[191] 
Dias V, Junn E, Mouradian MM. The role of oxidative stress in Parkinson’s disease. J Parkinsons Dis  2013; 3(4): 461-91.
[http://dx.doi.org/10.3233/JPD-130230] [PMID: 24252804] 
[192] 
Guzman JN, Sanchez-Padilla J, Wokosin D, et al. Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature  2010; 468(7324): 696-700.
[http://dx.doi.org/10.1038/nature09536] [PMID: 21068725] 
[193] 
Bolam JP, Pissadaki EK. Living on the edge with too many mouths to feed: why dopamine neurons die. Mov Disord  2012; 27(12): 1478-83.
[http://dx.doi.org/10.1002/mds.25135] [PMID: 23008164] 
[194] 
Dehay B, Bové J, Rodríguez-Muela N, et al. Pathogenic lysosomal depletion in Parkinson’s disease. J Neurosci  2010; 30(37): 12535-44.
[http://dx.doi.org/10.1523/JNEUROSCI.1920-10.2010] [PMID: 20844148] 
[195] 
Lotharius J, Brundin P. Pathogenesis of Parkinson’s disease: dopamine, vesicles and alpha-synuclein. Nat Rev Neurosci  2002; 3(12): 932-42.
[http://dx.doi.org/10.1038/nrn983] [PMID: 12461550] 
[196] 
Mosharov EV, Larsen KE, Kanter E, et al. Interplay between cytosolic dopamine, calcium, and alpha-synuclein causes selective death of substantia nigra neurons. Neuron  2009; 62(2): 218-29.
[http://dx.doi.org/10.1016/j.neuron.2009.01.033] [PMID: 19409267] 
[197] 
Pissadaki EK, Bolam JP. The energy cost of action potential propagation in dopamine neurons: clues to susceptibility in Parkinson’s disease. Front Comput Neurosci  2013; 7: 13.
[http://dx.doi.org/10.3389/fncom.2013.00013] [PMID: 23515615] 
[198] 
Hirsch EC, Hunot S. Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol  2009; 8(4): 382-97.
[http://dx.doi.org/10.1016/S1474-4422(09)70062-6] [PMID: 19296921] 
[199] 
Moehle MS, West AB. M1 and M2 immune activation in Parkinson’s Disease: Foe and ally? Neuroscience  2015; 302: 59-73.
[http://dx.doi.org/10.1016/j.neuroscience.2014.11.018] [PMID: 25463515] 
[200] 
Ransohoff RM. How neuroinflammation contributes to neurodegeneration. Science  2016; 353(6301): 777-83.
[http://dx.doi.org/10.1126/science.aag2590] [PMID: 27540165] 
[201] 
Gao HM, Kotzbauer PT, Uryu K, Leight S, Trojanowski JQ, Lee VM. Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration. J Neurosci  2008; 28(30): 7687-98.
[http://dx.doi.org/10.1523/JNEUROSCI.0143-07.2008] [PMID: 18650345] 
[202] 
Sampson T R, Debelius J W, Thron T, et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell  2016; 167: 1469-80.
[203] 
Coric V, van Dyck CH, Salloway S, et al. Safety and tolerability of the γ-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch Neurol  2012; 69(11): 1430-40.
[http://dx.doi.org/10.1001/archneurol.2012.2194] [PMID: 22892585] 
[204] 
Doody RS, Raman R, Farlow M, et al. Alzheimer’s Disease Cooperative Study Steering Committee; Semagacestat Study Group. A phase 3 trial of semagacestat for treatment of Alzheimer’s disease. N Engl J Med  2013; 369(4): 341-50.
[http://dx.doi.org/10.1056/NEJMoa1210951] [PMID: 23883379] 
[205] 
Doody RS, Thomas RG, Farlow M, et al. Alzheimer’s Disease Cooperative Study Steering Committee; Solanezumab Study Group. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med  2014; 370(4): 311-21.
[http://dx.doi.org/10.1056/NEJMoa1312889] [PMID: 24450890] 
[206] 
Galasko D, Bell J, Mancuso JY, et al. Alzheimer’s Disease Cooperative Study. Clinical trial of an inhibitor of RAGE-Aβ interactions in Alzheimer disease. Neurology  2014; 82(17): 1536-42.
[http://dx.doi.org/10.1212/WNL.0000000000000364] [PMID: 24696507] 
[207] 
Salloway S, Sperling R, Fox NC, et al. Bapineuzumab 301 and 302 Clinical Trial Investigators. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med  2014; 370(4): 322-33.
[http://dx.doi.org/10.1056/NEJMoa1304839] [PMID: 24450891] 
[208] 
Salloway S, Sperling R, Keren R, et al. ELND005-AD201 Investigators. A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. Neurology  2011; 77(13): 1253-62.
[http://dx.doi.org/10.1212/WNL.0b013e3182309fa5] [PMID: 21917766] 
[209] 
Mills SM, Mallmann J, Santacruz AM, et al. Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial. Rev Neurol (Paris)  2013; 169(10): 737-43.
[http://dx.doi.org/10.1016/j.neurol.2013.07.017] [PMID: 24016464] 
[210] 
Reiman EM, Langbaum JB, Fleisher AS, et al. Alzheimer’s Prevention Initiative: a plan to accelerate the evaluation of presymptomatic treatments. J Alzheimers Dis  2011; 26(Suppl. 3): 321-9.
[http://dx.doi.org/10.3233/JAD-2011-0059] [PMID: 21971471] 
[211] 
Roses AD, Saunders AM, Lutz MW, et al. New applications of disease genetics and pharmacogenetics to drug development. Curr Opin Pharmacol  2014; 14: 81-9.
[http://dx.doi.org/10.1016/j.coph.2013.12.002] [PMID: 24565016] 
[212] 
Moulder KL, Snider BJ, Mills SL, et al. Dominantly Inherited Alzheimer Network: facilitating research and clinical trials. Alzheimers Res Ther  2013; 5(5): 48.
[http://dx.doi.org/10.1186/alzrt213] [PMID: 24131566] 
[213] 
Langbaum JB, Fleisher AS, Chen K, et al. Ushering in the study and treatment of preclinical Alzheimer disease. Nat Rev Neurol  2013; 9(7): 371-81.
[http://dx.doi.org/10.1038/nrneurol.2013.107] [PMID: 23752908] 
[214] 
Claxton A, Baker LD, Hanson A, et al. Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer’s disease dementia. J Alzheimers Dis  2015; 44(3): 897-906.
[http://dx.doi.org/10.3233/JAD-141791] [PMID: 25374101] 
[215] 
Lyketsos CG, Targum SD, Pendergrass JC, Lozano AM. Deep brain stimulation: a novel strategy for treating Alzheimer’s disease. Innov Clin Neurosci  2012; 9(11-12): 10-7.
[PMID: 23346514] 
[216] 
Olde Rikkert MG, Verhey FR, Blesa R, et al. Tolerability and safety of Souvenaid in patients with mild Alzheimer’s disease: results of multi-center, 24-week, open-label extension study. J Alzheimers Dis  2015; 44(2): 471-80.
[http://dx.doi.org/10.3233/JAD-141305] [PMID: 25322923] 
[217] 
Sharma A, Bemis M, Desilets AR. Role of Medium Chain Triglycerides (Axona®) in the Treatment of Mild to Moderate Alzheimer’s Disease. Am J Alzheimers Dis Other Demen  2014; 29(5): 409-14.
[http://dx.doi.org/10.1177/1533317513518650] [PMID: 24413538] 
[218] 
Porsteinsson AP, Drye LT, Pollock BG, et al. CitAD Research Group. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA  2014; 311(7): 682-91.
[http://dx.doi.org/10.1001/jama.2014.93] [PMID: 24549548] 
[219] 
Yang LP, Deeks ED. Dextromethorphan/quinidine: a review of its use in adults with pseudobulbar affect. Drugs  2015; 75(1): 83-90.
[http://dx.doi.org/10.1007/s40265-014-0328-z] [PMID: 25420446] 
[220] 
Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet  2015; 385(9984): 2255-63.
[http://dx.doi.org/10.1016/S0140-6736(15)60461-5] [PMID: 25771249] 
[221] 
Ritchie CW, Ritchie K. The PREVENT study: a prospective cohort study to identify mid-life biomarkers of late-onset Alzheimer’s disease. BMJ Open  2012; 2(6): 2.
[http://dx.doi.org/10.1136/bmjopen-2012-001893] [PMID: 23166135] 
[222] 
AlDakheel A, Kalia LV, Lang AE. Pathogenesis-targeted, disease-modifying therapies in Parkinson disease. Neurotherapeutics  2014; 11(1): 6-23.
[http://dx.doi.org/10.1007/s13311-013-0218-1] [PMID: 24085420] 
[223] 
Tran HT, Chung CH, Iba M, et al. Α-synuclein immunotherapy blocks uptake and templated propagation of misfolded α-synuclein and neurodegeneration. Cell Rep  2014; 7(6): 2054-65.
[http://dx.doi.org/10.1016/j.celrep.2014.05.033] [PMID: 24931606] 
[224] 
Bjorklund A, Kordower JH. Cell therapy for Parkinson’s disease: what next? Mov Disord  2013; 28(1): 110-5.
[http://dx.doi.org/10.1002/mds.25343] [PMID: 23390097] 
[225] 
Charles D, Konrad PE, Neimat JS, et al. Subthalamic nucleus deep brain stimulation in early stage Parkinson’s disease. Parkinsonism Relat Disord  2014; 20(7): 731-7.
[http://dx.doi.org/10.1016/j.parkreldis.2014.03.019] [PMID: 24768120] 
[226] 
Coune PG, Schneider BL, Aebischer P. Parkinson’s disease: gene therapies. Cold Spring Harb Perspect Med  2012; 2(4): a009431.
[http://dx.doi.org/10.1101/cshperspect.a009431] [PMID: 22474617] 
[227] 
Kordower JH, Bjorklund A. Trophic factor gene therapy for Parkinson’s disease. Mov Disord  2013; 28(1): 96-109.
[http://dx.doi.org/10.1002/mds.25344] [PMID: 23390096] 
[228] 
Lindvall O. Developing dopaminergic cell therapy for Parkinson’s disease--give up or move forward? Mov Disord  2013; 28(3): 268-73.
[http://dx.doi.org/10.1002/mds.25378] [PMID: 23401015] 
[229] 
Agrawal AK, Chaturvedi RK, Shukla S, et al. Restorative potential of dopaminergic grafts in presence of antioxidants in rat model of Parkinson’s disease. J Chem Neuroanat  2004; 28(4): 253-64.
[http://dx.doi.org/10.1016/j.jchemneu.2004.08.001] [PMID: 15531136] 
[230] 
Agrawal AK, Shukla S, Chaturvedi RK, et al. Olfactory ensheathing cell transplantation restores functional deficits in rat model of Parkinson’s disease: a cotransplantation approach with fetal ventral mesencephalic cells. Neurobiol Dis  2004; 16(3): 516-26.
[http://dx.doi.org/10.1016/j.nbd.2004.04.014] [PMID: 15262263] 
[231] 
Chaturvedi RK, Agrawal AK, Seth K, et al. Effect of glial cell line-derived neurotrophic factor (GDNF) co-transplantation with fetal ventral mesencephalic cells (VMC) on functional restoration in 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson’s disease: neurobehavioral, neurochemical and immunohistochemical studies. Int J Dev Neurosci  2003; 21(7): 391-400.
[http://dx.doi.org/10.1016/S0736-5748(03)00087-X] [PMID: 14599485] 
[232] 
Chaturvedi RK, Shukla S, Seth K, Agrawal AK. Nerve growth factor increases survival of dopaminergic graft, rescue nigral dopaminergic neurons and restores functional deficits in rat model of Parkinson’s disease. Neurosci Lett  2006; 398(1-2): 44-9.
[http://dx.doi.org/10.1016/j.neulet.2005.12.042] [PMID: 16423459] 
[233] 
Chaturvedi RK, Shukla S, Seth K, Agrawal AK. Zuckerkandl’s organ improves long-term survival and function of neural stem cell derived dopaminergic neurons in Parkinsonian rats. Exp Neurol  2008; 210(2): 608-23.
[http://dx.doi.org/10.1016/j.expneurol.2007.12.016] [PMID: 18272152] 
[234] 
Shukla S, Agrawal AK, Chaturvedi RK, et al. Co-transplantation of carotid body and ventral mesencephalic cells as an alternative approach towards functional restoration in 6-hydroxydopamine-lesioned rats: implications for Parkinson’s disease. J Neurochem  2004; 91(2): 274-84.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02715.x] [PMID: 15447661] 
[235] 
Shukla S, Chaturvedi RK, Seth K, Roy NS, Agrawal AK. Enhanced survival and function of neural stem cells-derived dopaminergic neurons under influence of olfactory ensheathing cells in parkinsonian rats. J Neurochem  2009; 109(2): 436-51.
[http://dx.doi.org/10.1111/j.1471-4159.2009.05983.x] [PMID: 19222707] 
[236] 
Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA  2014; 311(16): 1670-83.
[http://dx.doi.org/10.1001/jama.2014.3654] [PMID: 24756517] 
[237] 
Lang AE, Marras C. Initiating dopaminergic treatment in Parkinson’s disease. Lancet  2014; 384(9949): 1164-6.
[http://dx.doi.org/10.1016/S0140-6736(14)60962-4] [PMID: 24928806] 
[238] 
Hauser RA, Hsu A, Kell S, et al. IPX066 ADVANCE-PD investigators. Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson’s disease and motor fluctuations: a phase 3 randomised, double-blind trial. Lancet Neurol  2013; 12(4): 346-56.
[http://dx.doi.org/10.1016/S1474-4422(13)70025-5] [PMID: 23485610] 
[239] 
Olanow CW, Kieburtz K, Odin P, et al. LCIG Horizon Study Group. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol  2014; 13(2): 141-9.
[http://dx.doi.org/10.1016/S1474-4422(13)70293-X] [PMID: 24361112] 
[240] 
Kalia LV, Brotchie JM, Fox SH. Novel nondopaminergic targets for motor features of Parkinson’s disease: review of recent trials. Mov Disord  2013; 28(2): 131-44.
[http://dx.doi.org/10.1002/mds.25273] [PMID: 23225267] 
[241] 
Burn D, Emre M, McKeith I, et al. Effects of rivastigmine in patients with and without visual hallucinations in dementia associated with Parkinson’s disease. Mov Disord  2006; 21(11): 1899-907.
[http://dx.doi.org/10.1002/mds.21077] [PMID: 16960863] 
[242] 
Honigfeld G, Arellano F, Sethi J, Bianchini A, Schein J. Reducing clozapine-related morbidity and mortality: 5 years of experience with the Clozaril National Registry. J Clin Psychiatry  1998; 59(Suppl. 3): 3-7.
[PMID: 9541331] 
[243] 
Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet  2014; 383(9916): 533-40.
[http://dx.doi.org/10.1016/S0140-6736(13)62106-6] [PMID: 24183563] 
[244] 
Barone P, Poewe W, Albrecht S, et al. Pramipexole for the treatment of depressive symptoms in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Neurol  2010; 9(6): 573-80.
[http://dx.doi.org/10.1016/S1474-4422(10)70106-X] [PMID: 20452823] 
[245] 
Richard IH, McDermott MP, Kurlan R, et al. SAD-PD Study Group. A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease. Neurology  2012; 78(16): 1229-36.
[http://dx.doi.org/10.1212/WNL.0b013e3182516244] [PMID: 22496199] 
[246] 
Yarnall A, Rochester L, Burn DJ. The interplay of cholinergic function, attention, and falls in Parkinson’s disease. Mov Disord  2011; 26(14): 2496-503.
[http://dx.doi.org/10.1002/mds.23932] [PMID: 21898597] 
[247] 
Emre M, Aarsland D, Albanese A, et al. Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med  2004; 351(24): 2509-18.
[http://dx.doi.org/10.1056/NEJMoa041470] [PMID: 15590953] 
[248] 
Henderson EJ, Lord SR, Close JC, Lawrence AD, Whone A, Ben-Shlomo Y. The ReSPonD trial--rivastigmine to stabilise gait in Parkinson’s disease a phase II, randomised, double blind, placebo controlled trial to evaluate the effect of rivastigmine on gait in patients with Parkinson’s disease who have fallen. BMC Neurol  2013; 13: 188.
[http://dx.doi.org/10.1186/1471-2377-13-188] [PMID: 24299497] 
[249] 
Chung KA, Lobb BM, Nutt JG, Horak FB. Effects of a central cholinesterase inhibitor on reducing falls in Parkinson disease. Neurology  2010; 75(14): 1263-9.
[http://dx.doi.org/10.1212/WNL.0b013e3181f6128c] [PMID: 20810998] 
[250] 
Kalia SK, Sankar T, Lozano AM. Deep brain stimulation for Parkinson’s disease and other movement disorders. Curr Opin Neurol  2013; 26(4): 374-80.
[http://dx.doi.org/10.1097/WCO.0b013e3283632d08] [PMID: 23817213] 
[251] 
Schuepbach WM, Rau J, Knudsen K, et al. EARLYSTIM Study Group. Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med  2013; 368(7): 610-22.
[http://dx.doi.org/10.1056/NEJMoa1205158] [PMID: 23406026] 
[252] 
Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis  2010; 37(1): 13-25.
[http://dx.doi.org/10.1016/j.nbd.2009.07.030] [PMID: 19664713] 
[253] 
Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci  2011; 12(12): 723-38.
[http://dx.doi.org/10.1038/nrn3114] [PMID: 22048062] 
[254] 
Bell RD, Winkler EA, Sagare AP, et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron  2010; 68(3): 409-27.
[http://dx.doi.org/10.1016/j.neuron.2010.09.043] [PMID: 21040844] 
[255] 
Deane R, Zlokovic BV. Role of the blood-brain barrier in the pathogenesis of Alzheimer’s disease. Curr Alzheimer Res  2007; 4(2): 191-7.
[http://dx.doi.org/10.2174/156720507780362245] [PMID: 17430246] 
[256] 
Erickson MA, Banks WA. Blood-brain barrier dysfunction as a cause and consequence of Alzheimer’s disease. J Cereb Blood Flow Metab  2013; 33(10): 1500-13.
[http://dx.doi.org/10.1038/jcbfm.2013.135] [PMID: 23921899] 
[257] 
Zhao Z, Nelson AR, Betsholtz C, Zlokovic BV. Establishment and Dysfunction of the Blood-Brain Barrier. Cell  2015; 163(5): 1064-78.
[http://dx.doi.org/10.1016/j.cell.2015.10.067] [PMID: 26590417] 
[258] 
Arvanitakis Z, Capuano AW, Leurgans SE, Bennett DA, Schneider JA. Relation of cerebral vessel disease to Alzheimer’s disease dementia and cognitive function in elderly people: a cross-sectional study. Lancet Neurol  2016; 15(9): 934-43.
[http://dx.doi.org/10.1016/S1474-4422(16)30029-1] [PMID: 27312738] 
[259] 
Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci  1991; 12(10): 383-8.
[http://dx.doi.org/10.1016/0165-6147(91)90609-V] [PMID: 1763432] 
[260] 
Saito S, Ihara M. Interaction between cerebrovascular disease and Alzheimer pathology. Curr Opin Psychiatry  2016; 29(2): 168-73.
[http://dx.doi.org/10.1097/YCO.0000000000000239] [PMID: 26779861] 
[261] 
Nelson AR, Sweeney MD, Sagare AP, Zlokovic BV. Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer’s disease. Biochim Biophys Acta  2016; 1862(5): 887-900.
[http://dx.doi.org/10.1016/j.bbadis.2015.12.016] [PMID: 26705676] 
[262] 
Sweeney MD, Sagare AP, Zlokovic BV. Cerebrospinal fluid biomarkers of neurovascular dysfunction in mild dementia and Alzheimer’s disease. J Cereb Blood Flow Metab  2015; 35(7): 1055-68.
[http://dx.doi.org/10.1038/jcbfm.2015.76] [PMID: 25899298] 
[263] 
Goos JD, Kester MI, Barkhof F, et al. Patients with Alzheimer disease with multiple microbleeds: relation with cerebrospinal fluid biomarkers and cognition. Stroke  2009; 40(11): 3455-60.
[http://dx.doi.org/10.1161/STROKEAHA.109.558197] [PMID: 19762705] 
[264] 
Heringa SM, Reijmer YD, Leemans A, Koek HL, Kappelle LJ, Biessels GJ. Utrecht Vascular Cognitive Impairment (VCI) Study Group. Multiple microbleeds are related to cerebral network disruptions in patients with early Alzheimer’s disease. J Alzheimers Dis  2014; 38(1): 211-21.
[http://dx.doi.org/10.3233/JAD-130542] [PMID: 23948936] 
[265] 
Yates PA, Desmond PM, Phal PM, et al. AIBL Research Group. Incidence of cerebral microbleeds in preclinical Alzheimer disease. Neurology  2014; 82(14): 1266-73.
[http://dx.doi.org/10.1212/WNL.0000000000000285] [PMID: 24623839] 
[266] 
Kantarci K, Gunter JL, Tosakulwong N, et al. Alzheimer’s Disease Neuroimaging Initiative. Focal hemosiderin deposits and β-amyloid load in the ADNI cohort. Alzheimers Dement  2013; 9(5)(Suppl.): S116-23.
[http://dx.doi.org/10.1016/j.jalz.2012.10.011] [PMID: 23375568] 
[267] 
Mosconi L, Sorbi S, de Leon MJ, et al. Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer’s disease. J Nucl Med  2006; 47(11): 1778-86.
[PMID: 17079810] 
[268] 
Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement  2011; 7(3): 280-92.
[http://dx.doi.org/10.1016/j.jalz.2011.03.003] [PMID: 21514248] 
[269] 
Winkler EA, Nishida Y, Sagare AP, et al. GLUT1 reductions exacerbate Alzheimer’s disease vasculo-neuronal dysfunction and degeneration. Nat Neurosci  2015; 18(4): 521-30.
[http://dx.doi.org/10.1038/nn.3966] [PMID: 25730668] 
[270] 
Deo AK, Borson S, Link JM, et al. Activity of P-Glycoprotein, a β-Amyloid Transporter at the Blood-Brain Barrier, Is Compromised in Patients with Mild Alzheimer Disease. J Nucl Med  2014; 55(7): 1106-11.
[http://dx.doi.org/10.2967/jnumed.113.130161] [PMID: 24842892] 
[271] 
Hultman K, Strickland S, Norris EH. The APOE varepsilon4/varepsilon4 genotype potentiates vascular fibrin(ogen) deposition in amyloid-laden vessels in the brains of Alzheimer’s disease patients. J Cereb Blood Flow Metab  2013; 33: 1251-8.
[http://dx.doi.org/10.1038/jcbfm.2013.76] [PMID: 23652625] 
[272] 
Zenaro E, Pietronigro E, Della Bianca V, et al. Neutrophils promote Alzheimer’s disease-like pathology and cognitive decline via LFA-1 integrin. Nat Med  2015; 21(8): 880-6.
[http://dx.doi.org/10.1038/nm.3913] [PMID: 26214837] 
[273] 
Kortekaas R, Leenders KL, van Oostrom JC, et al. Blood-brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol  2005; 57(2): 176-9.
[http://dx.doi.org/10.1002/ana.20369] [PMID: 15668963] 
[274] 
Pisani V, Stefani A, Pierantozzi M, et al. Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson’s disease. J Neuroinflammation  2012; 9: 188.
[http://dx.doi.org/10.1186/1742-2094-9-188] [PMID: 22870899] 
[275] 
Gray MT, Woulfe JM. Striatal blood-brain barrier permeability in Parkinson’s disease. J Cereb Blood Flow Metab  2015; 35(5): 747-50.
[http://dx.doi.org/10.1038/jcbfm.2015.32] [PMID: 25757748] 
[276] 
Brochard V, Combadière B, Prigent A, et al. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest  2009; 119(1): 182-92.
[PMID: 19104149] 
[277] 
Carvey PM, Zhao CH, Hendey B, et al. 6-Hydroxydopamine-induced alterations in blood-brain barrier permeability. Eur J Neurosci  2005; 22(5): 1158-68.
[http://dx.doi.org/10.1111/j.1460-9568.2005.04281.x] [PMID: 16176358] 
[278] 
Chen B, Friedman B, Cheng Q, et al. Severe blood-brain barrier disruption and surrounding tissue injury. Stroke  2009; 40(12): e666-74.
[http://dx.doi.org/10.1161/STROKEAHA.109.551341] [PMID: 19893002] 
[279] 
Banks WA. From blood-brain barrier to blood-brain interface: new opportunities for CNS drug delivery. Nat Rev Drug Discov  2016; 15(4): 275-92.
[http://dx.doi.org/10.1038/nrd.2015.21] [PMID: 26794270] 
[280] 
Brownson EA, Abbruscato TJ, Gillespie TJ, Hruby VJ, Davis TP. Effect of peptidases at the blood brain barrier on the permeability of enkephalin. J Pharmacol Exp Ther  1994; 270(2): 675-80.
[PMID: 7915319] 
[281] 
Grubb JH, Vogler C, Levy B, Galvin N, Tan Y, Sly WS. Chemically modified beta-glucuronidase crosses blood-brain barrier and clears neuronal storage in murine mucopolysaccharidosis VII. Proc Natl Acad Sci USA  2008; 105(7): 2616-21.
[http://dx.doi.org/10.1073/pnas.0712147105] [PMID: 18268347] 
[282] 
Novakovic ZM, Anderson BM, Grasso P. Myristic acid conjugation of [D-Leu-4]-OB3, a biologically active leptin-related synthetic peptide amide, significantly improves its pharmacokinetic profile and efficacy. Peptides  2014; 62: 176-82.
[http://dx.doi.org/10.1016/j.peptides.2014.10.007] [PMID: 25453979] 
[283] 
Webster TJ. Nanomedicine: what’s in a definition? Int J Nanomedicine  2006; 1(2): 115-6.
[http://dx.doi.org/10.2147/nano.2006.1.2.115] [PMID: 17722527] 
[284] 
Min Y, Caster J M, Eblan M J, Wang A Z. Clinical Translation of Nanomedicine. Chem Rev  2015; 115: 11147-90.
[285] 
Cho EJ, Holback H, Liu KC, Abouelmagd SA, Park J, Yeo Y. Nanoparticle characterization: state of the art, challenges, and emerging technologies. Mol Pharm  2013; 10(6): 2093-110.
[http://dx.doi.org/10.1021/mp300697h] [PMID: 23461379] 
[286] 
Machado S, Pacheco JG, Nouws HP, Albergaria JT, Delerue-Matos C. Characterization of green zero-valent iron nanoparticles produced with tree leaf extracts. Sci Total Environ  2015; 533: 76-81.
[http://dx.doi.org/10.1016/j.scitotenv.2015.06.091] [PMID: 26151651] 
[287] 
Redhead HM, Davis SS, Illum L. Drug delivery in poly(lactide-co-glycolide) nanoparticles surface modified with poloxamer 407 and poloxamine 908: in vitro characterisation and in vivo evaluation. J Control Release  2001; 70(3): 353-63.
[http://dx.doi.org/10.1016/S0168-3659(00)00367-9] [PMID: 11182205] 
[288] 
Otsuka H, Nagasaki Y, Kataoka K. PEGylated nanoparticles for biological and pharmaceutical applications. Adv Drug Deliv Rev  2003; 55(3): 403-19.
[http://dx.doi.org/10.1016/S0169-409X(02)00226-0] [PMID: 12628324] 
[289] 
McDevitt MR, Chattopadhyay D, Kappel BJ, et al. Tumor targeting with antibody-functionalized, radiolabeled carbon nanotubes. J Nucl Med  2007; 48(7): 1180-9.
[http://dx.doi.org/10.2967/jnumed.106.039131] [PMID: 17607040] 
[290] 
Prato M, Kostarelos K, Bianco A. Functionalized carbon nanotubes in drug design and discovery. Acc Chem Res  2008; 41(1): 60-8.
[http://dx.doi.org/10.1021/ar700089b] [PMID: 17867649] 
[291] 
Acharya R, Saha S, Ray S, Hazra S, Mitra MK, Chakraborty J. siRNA-nanoparticle conjugate in gene silencing: A future cure to deadly diseases? Mater Sci Eng C  2017; 76: 1378-400.
[http://dx.doi.org/10.1016/j.msec.2017.03.009] [PMID: 28482505] 
[292] 
Zhang Z, Yang X, Zhang Y, et al. Delivery of telomerase reverse transcriptase small interfering RNA in complex with positively charged single-walled carbon nanotubes suppresses tumor growth. Clin Cancer Res  2006; 12(16): 4933-9.
[http://dx.doi.org/10.1158/1078-0432.CCR-05-2831] [PMID: 16914582] 
[293] 
Zheng M, Tao W, Zou Y, Farokhzad OC, Shi B. Nanotechnology-Based Strategies for siRNA Brain Delivery for Disease Therapy. Trends Biotechnol  2018; 36(5): 562-75.
[http://dx.doi.org/10.1016/j.tibtech.2018.01.006] [PMID: 29422412] 
[294] 
Sinha N, Yeow JT. Carbon nanotubes for biomedical applications. IEEE Trans Nanobioscience  2005; 4(2): 180-95.
[http://dx.doi.org/10.1109/TNB.2005.850478] [PMID: 16117026] 
[295] 
Xue X, Yang JY, He Y, et al. Aggregated single-walled carbon nanotubes attenuate the behavioural and neurochemical effects of methamphetamine in mice. Nat Nanotechnol  2016; 11(7): 613-20.
[http://dx.doi.org/10.1038/nnano.2016.23] [PMID: 26974957] 
[296] 
Yang Z, Zhang Y, Yang Y, et al. Pharmacological and toxicological target organelles and safe use of single-walled carbon nanotubes as drug carriers in treating Alzheimer disease. Nanomedicine (Lond)  2010; 6(3): 427-41.
[http://dx.doi.org/10.1016/j.nano.2009.11.007] [PMID: 20056170] 
[297] 
Bosi S, Da Ros T, Castellano S, Banfi E, Prato M. Antimycobacterial activity of ionic fullerene derivatives. Bioorg Med Chem Lett  2000; 10(10): 1043-5.
[http://dx.doi.org/10.1016/S0960-894X(00)00159-1] [PMID: 10843212] 
[298] 
Ji H, Yang Z, Jiang W, et al. Antiviral activity of nano carbon fullerene lipidosome against influenza virus in vitro. J Huazhong Univ Sci Technolog Med Sci  2008; 28(3): 243-6.
[http://dx.doi.org/10.1007/s11596-008-0303-6] [PMID: 18563315] 
[299] 
Mroz P, Pawlak A, Satti M, et al. Functionalized fullerenes mediate photodynamic killing of cancer cells: Type I versus Type II photochemical mechanism. Free Radic Biol Med  2007; 43(5): 711-9.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.05.005] [PMID: 17664135] 
[300] 
Tegos GP, Demidova TN, Arcila-Lopez D, et al. Cationic fullerenes are effective and selective antimicrobial photosensitizers. Chem Biol  2005; 12(10): 1127-35.
[http://dx.doi.org/10.1016/j.chembiol.2005.08.014] [PMID: 16242655] 
[301] 
Cai X, Jia H, Liu Z, et al. Polyhydroxylated fullerene derivative C(60)(OH)(24) prevents mitochondrial dysfunction and oxidative damage in an MPP(+) -induced cellular model of Parkinson’s disease. J Neurosci Res  2008; 86(16): 3622-34.
[http://dx.doi.org/10.1002/jnr.21805] [PMID: 18709653] 
[302] 
Markovic Z, Trajkovic V. Biomedical potential of the reactive oxygen species generation and quenching by fullerenes (C60). Biomaterials  2008; 29(26): 3561-73.
[http://dx.doi.org/10.1016/j.biomaterials.2008.05.005] [PMID: 18534675] 
[303] 
Dugan LL, Lovett EG, Quick KL, Lotharius J, Lin TT, O’Malley KL. Fullerene-based antioxidants and neurodegenerative disorders. Parkinsonism Relat Disord  2001; 7(3): 243-6.
[http://dx.doi.org/10.1016/S1353-8020(00)00064-X] [PMID: 11331193] 
[304] 
Chen BX, Wilson SR, Das M, Coughlin DJ, Erlanger BF. Antigenicity of fullerenes: antibodies specific for fullerenes and their characteristics. Proc Natl Acad Sci USA  1998; 95(18): 10809-13.
[http://dx.doi.org/10.1073/pnas.95.18.10809] [PMID: 9724786] 
[305] 
Gao X, Cui Y, Levenson RM, Chung LW, Nie S. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol  2004; 22(8): 969-76.
[http://dx.doi.org/10.1038/nbt994] [PMID: 15258594] 
[306] 
Ma W, Qin LX, Liu FT, et al. Ubiquinone-quantum dot bioconjugates for in vitro and intracellular complex I sensing. Sci Rep  2013; 3: 1537.
[http://dx.doi.org/10.1038/srep01537] [PMID: 23524384] 
[307] 
Tokuraku K, Marquardt M, Ikezu T. Real-time imaging and quantification of amyloid-beta peptide aggregates by novel quantum-dot nanoprobes. PLoS One  2009; 4(12): e8492.
[http://dx.doi.org/10.1371/journal.pone.0008492] [PMID: 20041162] 
[308] 
West JL, Halas NJ. Applications of nanotechnology to biotechnology commentary. Curr Opin Biotechnol  2000; 11(2): 215-7.
[http://dx.doi.org/10.1016/S0958-1669(00)00082-3] [PMID: 10753774] 
[309] 
Kherlopian AR, Song T, Duan Q, et al. A review of imaging techniques for systems biology. BMC Syst Biol  2008; 2: 74.
[http://dx.doi.org/10.1186/1752-0509-2-74] [PMID: 18700030] 
[310] 
Gao Z, Kennedy AM, Christensen DA, Rapoport NY. Drug-loaded nano/microbubbles for combining ultrasonography and targeted chemotherapy. Ultrasonics  2008; 48(4): 260-70.
[http://dx.doi.org/10.1016/j.ultras.2007.11.002] [PMID: 18096196] 
[311] 
Klibanov AL. Microbubble contrast agents: targeted ultrasound imaging and ultrasound-assisted drug-delivery applications. Invest Radiol  2006; 41(3): 354-62.
[http://dx.doi.org/10.1097/01.rli.0000199292.88189.0f] [PMID: 16481920] 
[312] 
Negishi Y, Endo Y, Fukuyama T, et al. Delivery of siRNA into the cytoplasm by liposomal bubbles and ultrasound. J Control Release  2008; 132(2): 124-30.
[http://dx.doi.org/10.1016/j.jconrel.2008.08.019] [PMID: 18804499] 
[313] 
Suzuki R, Takizawa T, Negishi Y, Utoguchi N, Maruyama K. Effective gene delivery with novel liposomal bubbles and ultrasonic destruction technology. Int J Pharm  2008; 354(1-2): 49-55.
[http://dx.doi.org/10.1016/j.ijpharm.2007.10.034] [PMID: 18082343] 
[314] 
Iverson N, Plourde N, Chnari E, Nackman GB, Moghe PV. Convergence of nanotechnology and cardiovascular medicine : progress and emerging prospects. BioDrugs  2008; 22(1): 1-10.
[http://dx.doi.org/10.2165/00063030-200822010-00001] [PMID: 18215086] 
[315] 
Hwang TL, Lin YK, Chi CH, Huang TH, Fang JY. Development and evaluation of perfluorocarbon nanobubbles for apomorphine delivery. J Pharm Sci  2009; 98(10): 3735-47.
[http://dx.doi.org/10.1002/jps.21687] [PMID: 19156914] 
[316] 
Artemov D, Mori N, Okollie B, Bhujwalla ZM. MR molecular imaging of the Her-2/neu receptor in breast cancer cells using targeted iron oxide nanoparticles. Magn Reson Med  2003; 49(3): 403-8.
[http://dx.doi.org/10.1002/mrm.10406] [PMID: 12594741] 
[317] 
Nam JM, Thaxton CS, Mirkin CA. Nanoparticle-based bio-bar codes for the ultrasensitive detection of proteins. Science  2003; 301(5641): 1884-6.
[http://dx.doi.org/10.1126/science.1088755] [PMID: 14512622] 
[318] 
Moore A, Weissleder R, Bogdanov A Jr. Uptake of dextran-coated monocrystalline iron oxides in tumor cells and macrophages. J Magn Reson Imaging  1997; 7(6): 1140-5.
[http://dx.doi.org/10.1002/jmri.1880070629] [PMID: 9400860] 
[319] 
Yang SY, Chiu MJ, Lin CH, et al. Development of an ultra-high sensitive immunoassay with plasma biomarker for differentiating Parkinson disease dementia from Parkinson disease using antibody functionalized magnetic nanoparticles. J Nanobiotechnology  2016; 14(1): 41.
[http://dx.doi.org/10.1186/s12951-016-0198-5] [PMID: 27278241] 
[320] 
Zhang D, Fa HB, Zhou JT, Li S, Diao XW, Yin W. The detection of β-amyloid plaques in an Alzheimer’s disease rat model with DDNP-SPIO. Clin Radiol  2015; 70(1): 74-80.
[http://dx.doi.org/10.1016/j.crad.2014.09.019] [PMID: 25459675] 
[321] 
Xu H, Yan F, Monson EE, Kopelman R. Room-temperature preparation and characterization of poly (ethylene glycol)-coated silica nanoparticles for biomedical applications. J Biomed Mater Res A  2003; 66(4): 870-9.
[http://dx.doi.org/10.1002/jbm.a.10057] [PMID: 12926040] 
[322] 
Freitas RA Jr. Pharmacytes: an ideal vehicle for targeted drug delivery. J Nanosci Nanotechnol  2006; 6(9-10): 2769-75.
[http://dx.doi.org/10.1166/jnn.2006.413] [PMID: 17048481] 
[323] 
Moghimi SM, Hunter AC, Murray JC. Nanomedicine: current status and future prospects. FASEB J  2005; 19(3): 311-30.
[http://dx.doi.org/10.1096/fj.04-2747rev] [PMID: 15746175] 
[324] 
Tomalia DA, Reyna LA, Svenson S. Dendrimers as multi-purpose nanodevices for oncology drug delivery and diagnostic imaging. Biochem Soc Trans  2007; 35(Pt 1): 61-7.
[http://dx.doi.org/10.1042/BST0350061] [PMID: 17233602] 
[325] 
Huang R, Han L, Li J, et al. Neuroprotection in a 6-hydroxydopamine-lesioned Parkinson model using lactoferrin-modified nanoparticles. J Gene Med  2009; 11(9): 754-63.
[http://dx.doi.org/10.1002/jgm.1361] [PMID: 19554623] 
[326] 
Onoue S, Terasawa N, Nakamura T, Yuminoki K, Hashimoto N, Yamada S. Biopharmaceutical characterization of nanocrystalline solid dispersion of coenzyme Q10 prepared with cold wet-milling system. Eur J Pharm Sci  2014; 53: 118-25.
[http://dx.doi.org/10.1016/j.ejps.2013.12.013] [PMID: 24368114] 
[327] 
Tsai MJ, Huang YB, Wu PC, et al. Oral apomorphine delivery from solid lipid nanoparticles with different monostearate emulsifiers: pharmacokinetic and behavioral evaluations. J Pharm Sci  2011; 100(2): 547-57.
[http://dx.doi.org/10.1002/jps.22285] [PMID: 20740670] 
[328] 
Son D, Lee J, Qiao S, et al. Multifunctional wearable devices for diagnosis and therapy of movement disorders. Nat Nanotechnol  2014; 9(5): 397-404.
[http://dx.doi.org/10.1038/nnano.2014.38] [PMID: 24681776] 
[329] 
Choi JS, Choi HJ, Jung DC, Lee JH, Cheon J. Nanoparticle assisted magnetic resonance imaging of the early reversible stages of amyloid beta self-assembly. Chem Commun (Camb)  2008; (19): 2197-9.
[http://dx.doi.org/10.1039/b803294g] [PMID: 18463738] 
[330] 
Yu X, He X, Yang T, et al. Sensitive determination of dopamine levels via surface-enhanced Raman scattering of Ag nanoparticle dimers. Int J Nanomedicine  2018; 13: 2337-47.
[http://dx.doi.org/10.2147/IJN.S156932] [PMID: 29713165] 
[331] 
Ismail MF, Elmeshad AN, Salem NA. Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer’s disease. Int J Nanomedicine  2013; 8: 393-406.
[http://dx.doi.org/10.2147/IJN.S39232] [PMID: 23378761] 
[332] 
Migliore MM, Ortiz R, Dye S, Campbell RB, Amiji MM, Waszczak BL. Neurotrophic and neuroprotective efficacy of intranasal GDNF in a rat model of Parkinson’s disease. Neuroscience  2014; 274: 11-23.
[http://dx.doi.org/10.1016/j.neuroscience.2014.05.019] [PMID: 24845869] 
[333] 
Lu X, Ji C, Xu H, et al. Resveratrol-loaded polymeric micelles protect cells from Abeta-induced oxidative stress. Int J Pharm  2009; 375(1-2): 89-96.
[http://dx.doi.org/10.1016/j.ijpharm.2009.03.021] [PMID: 19481694] 
[334] 
Martinez-Fong D, Bannon MJ, Trudeau LE, et al. NTS-Polyplex: a potential nanocarrier for neurotrophic therapy of Parkinson’s disease. Nanomedicine (Lond)  2012; 8(7): 1052-69.
[http://dx.doi.org/10.1016/j.nano.2012.02.009] [PMID: 22406187] 
[335] 
Fazil M, Md S, Haque S, et al. Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting. Eur J Pharm Sci  2012; 47(1): 6-15.
[http://dx.doi.org/10.1016/j.ejps.2012.04.013] [PMID: 22561106] 
[336] 
Md S, Khan RA, Mustafa G, et al. Bromocriptine loaded chitosan nanoparticles intended for direct nose to brain delivery: pharmacodynamic, pharmacokinetic and scintigraphy study in mice model. Eur J Pharm Sci  2013; 48(3): 393-405.
[http://dx.doi.org/10.1016/j.ejps.2012.12.007] [PMID: 23266466] 
[337] 
Andreasen N, Minthon L, Davidsson P, et al. Evaluation of CSF-tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice. Arch Neurol  2001; 58(3): 373-9.
[http://dx.doi.org/10.1001/archneur.58.3.373] [PMID: 11255440] 
[338] 
Hulstaert F, Blennow K, Ivanoiu A, et al. Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF. Neurology  1999; 52(8): 1555-62.
[http://dx.doi.org/10.1212/WNL.52.8.1555] [PMID: 10331678] 
[339] 
Maddalena A, Papassotiropoulos A, Müller-Tillmanns B, et al. Biochemical diagnosis of Alzheimer disease by measuring the cerebrospinal fluid ratio of phosphorylated tau protein to beta-amyloid peptide42. Arch Neurol  2003; 60(9): 1202-6.
[http://dx.doi.org/10.1001/archneur.60.9.1202] [PMID: 12975284] 
[340] 
Georganopoulou DG, Chang L, Nam JM, et al. Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer’s disease. Proc Natl Acad Sci USA  2005; 102(7): 2273-6.
[http://dx.doi.org/10.1073/pnas.0409336102] [PMID: 15695586] 
[341] 
Moghimi SM. Bionanotechnologies for treatment and diagnosis of Alzheimer’s disease. Nanomedicine (Lond)  2011; 7(5): 515-8.
[http://dx.doi.org/10.1016/j.nano.2011.05.001] [PMID: 21616169] 
[342] 
Kang DY, Lee JH, Oh BK, Choi JW. Ultra-sensitive immunosensor for beta-amyloid (1-42) using scanning tunneling microscopy-based electrical detection. Biosens Bioelectron  2009; 24(5): 1431-6.
[http://dx.doi.org/10.1016/j.bios.2008.08.018] [PMID: 18829296] 
[343] 
Neely A, Perry C, Varisli B, et al. Ultrasensitive and highly selective detection of Alzheimer’s disease biomarker using two-photon Rayleigh scattering properties of gold nanoparticle. ACS Nano  2009; 3(9): 2834-40.
[http://dx.doi.org/10.1021/nn900813b] [PMID: 19691350] 
[344] 
Viola KL, Sbarboro J, Sureka R, et al. Towards non-invasive diagnostic imaging of early-stage Alzheimer’s disease. Nat Nanotechnol  2015; 10(1): 91-8.
[http://dx.doi.org/10.1038/nnano.2014.254] [PMID: 25531084] 
[345] 
Wadghiri YZ, Sigurdsson EM, Sadowski M, et al. Detection of Alzheimer’s amyloid in transgenic mice using magnetic resonance microimaging. Magn Reson Med  2003; 50(2): 293-302.
[http://dx.doi.org/10.1002/mrm.10529] [PMID: 12876705] 
[346] 
Yang J, Wadghiri YZ, Hoang DM, et al. Detection of amyloid plaques targeted by USPIO-Aβ1-42 in Alzheimer’s disease transgenic mice using magnetic resonance microimaging. Neuroimage  2011; 55(4): 1600-9.
[http://dx.doi.org/10.1016/j.neuroimage.2011.01.023] [PMID: 21255656] 
[347] 
Sillerud LO, Solberg NO, Chamberlain R, et al. SPION-enhanced magnetic resonance imaging of Alzheimer’s disease plaques in AβPP/PS-1 transgenic mouse brain. J Alzheimers Dis  2013; 34(2): 349-65.
[http://dx.doi.org/10.3233/JAD-121171] [PMID: 23229079] 
[348] 
Jaruszewski KM, Curran GL, Swaminathan SK, et al. Multimodal nanoprobes to target cerebrovascular amyloid in Alzheimer’s disease brain. Biomaterials  2014; 35(6): 1967-76.
[http://dx.doi.org/10.1016/j.biomaterials.2013.10.075] [PMID: 24331706] 
[349] 
Plissonneau M, Pansieri J, Heinrich-Balard L, et al. Gd-nanoparticles functionalization with specific peptides for ß-amyloid plaques targeting. J Nanobiotechnology  2016; 14(1): 60.
[http://dx.doi.org/10.1186/s12951-016-0212-y] [PMID: 27455834] 
[350] 
Nesterov EE, Skoch J, Hyman BT, Klunk WE, Bacskai BJ, Swager TM. In vivo optical imaging of amyloid aggregates in brain: design of fluorescent markers. Angew Chem Int Ed Engl  2005; 44(34): 5452-6.
[http://dx.doi.org/10.1002/anie.200500845] [PMID: 16059955] 
[351] 
Henley DB, May PC, Dean RA, Siemers ER. Development of semagacestat (LY450139), a functional gamma-secretase inhibitor, for the treatment of Alzheimer’s disease. Expert Opin Pharmacother  2009; 10(10): 1657-64.
[http://dx.doi.org/10.1517/14656560903044982] [PMID: 19527190] 
[352] 
Akhter S, Ahmad Z, Singh A, et al. Cancer targeted metallic nanoparticle: targeting overview, recent advancement and toxicity concern. Curr Pharm Des  2011; 17(18): 1834-50.
[http://dx.doi.org/10.2174/138161211796391001] [PMID: 21568874] 
[353] 
Alam Q, ZubairAlam M, Karim S, et al. A nanotechnological approach to the management of Alzheimer disease and type 2 diabetes. CNS Neurol Disord Drug Targets  2014; 13(3): 478-86.
[http://dx.doi.org/10.2174/18715273113126660159] [PMID: 24059303] 
[354] 
Dubertret B, Skourides P, Norris DJ, Noireaux V, Brivanlou AH, Libchaber A. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science  2002; 298(5599): 1759-62.
[http://dx.doi.org/10.1126/science.1077194] [PMID: 12459582] 
[355] 
Xu G, Yong KT, Roy I, et al. Bioconjugated quantum rods as targeted probes for efficient transmigration across an in vitro blood-brain barrier. Bioconjug Chem  2008; 19(6): 1179-85.
[http://dx.doi.org/10.1021/bc700477u] [PMID: 18473444] 
[356] 
Haziza S, Mohan N, Loe-Mie Y, et al. Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors. Nat Nanotechnol  2017; 12(4): 322-8.
[http://dx.doi.org/10.1038/nnano.2016.260] [PMID: 27893730] 
[357] 
Yue HY, Huang S, Chang J, et al. ZnO nanowire arrays on 3D hierachical graphene foam: biomarker detection of Parkinson’s disease. ACS Nano  2014; 8(2): 1639-46.
[http://dx.doi.org/10.1021/nn405961p] [PMID: 24405012] 
[358] 
Kurzatkowska K, Dolusic E, Dehaen W, Sieroń-Stołtny K, Sieroń A, Radecka H. Gold electrode incorporating corrole as an ion-channel mimetic sensor for determination of dopamine. Anal Chem  2009; 81(17): 7397-405.
[http://dx.doi.org/10.1021/ac901213h] [PMID: 19637903] 
[359] 
An Y, Tang L, Jiang X, et al. A photoelectrochemical immunosensor based on Au-doped TiO2 nanotube arrays for the detection of α-synuclein. Chemistry  2010; 16(48): 14439-46.
[http://dx.doi.org/10.1002/chem.201001654] [PMID: 21038326] 
[360] 
Broza YY, Haick H. Nanomaterial-based sensors for detection of disease by volatile organic compounds. Nanomedicine (Lond)  2013; 8(5): 785-806.
[http://dx.doi.org/10.2217/nnm.13.64] [PMID: 23656265] 
[361] 
Tisch U, Schlesinger I, Ionescu R, et al. Detection of Alzheimer’s and Parkinson’s disease from exhaled breath using nanomaterial-based sensors. Nanomedicine (Lond)  2013; 8(1): 43-56.
[http://dx.doi.org/10.2217/nnm.12.105] [PMID: 23067372] 
[362] 
Ortega R, Cloetens P, Devès G, Carmona A, Bohic S. Iron storage within dopamine neurovesicles revealed by chemical nano-imaging. PLoS One  2007; 2(9): e925.
[http://dx.doi.org/10.1371/journal.pone.0000925] [PMID: 17895967] 
[363] 
Geers B, Lentacker I, Sanders NN, Demeester J, Meairs S, De Smedt SC. Self-assembled liposome-loaded microbubbles: The missing link for safe and efficient ultrasound triggered drug-delivery. J Control Release  2011; 152(2): 249-56.
[http://dx.doi.org/10.1016/j.jconrel.2011.02.024] [PMID: 21362448] 
[364] 
Wang X, Cui G, Yang X, et al. Intracerebral administration of ultrasound-induced dissolution of lipid-coated GDNF microbubbles provides neuroprotection in a rat model of Parkinson’s disease. Brain Res Bull  2014; 103: 60-5.
[http://dx.doi.org/10.1016/j.brainresbull.2014.02.006] [PMID: 24583079] 
[365] 
Veiseh O, Gunn JW, Zhang M. Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv Drug Deliv Rev  2010; 62(3): 284-304.
[http://dx.doi.org/10.1016/j.addr.2009.11.002] [PMID: 19909778] 
[366] 
McLaurin J, Franklin T, Zhang X, Deng J, Fraser PE. Interactions of Alzheimer amyloid-beta peptides with glycosaminoglycans effects on fibril nucleation and growth. Eur J Biochem  1999; 266(3): 1101-10.
[http://dx.doi.org/10.1046/j.1432-1327.1999.00957.x] [PMID: 10583407] 
[367] 
Ikeda K, Okada T, Sawada S, Akiyoshi K, Matsuzaki K. Inhibition of the formation of amyloid beta-protein fibrils using biocompatible nanogels as artificial chaperones. FEBS Lett  2006; 580(28-29): 6587-95.
[http://dx.doi.org/10.1016/j.febslet.2006.11.009] [PMID: 17125770] 
[368] 
Boridy S, Takahashi H, Akiyoshi K, Maysinger D. The binding of pullulan modified cholesteryl nanogels to Abeta oligomers and their suppression of cytotoxicity. Biomaterials  2009; 30(29): 5583-91.
[http://dx.doi.org/10.1016/j.biomaterials.2009.06.010] [PMID: 19577802] 
[369] 
Dugan LL, Gabrielsen JK, Yu SP, Lin TS, Choi DW. Buckminsterfullerenol free radical scavengers reduce excitotoxic and apoptotic death of cultured cortical neurons. Neurobiol Dis  1996; 3(2): 129-35.
[http://dx.doi.org/10.1006/nbdi.1996.0013] [PMID: 9173920] 
[370] 
Huang HM, Ou HC, Hsieh SJ, Chiang LY. Blockage of amyloid beta peptide-induced cytosolic free calcium by fullerenol-1, carboxylate C60 in PC12 cells. Life Sci  2000; 66(16): 1525-33.
[http://dx.doi.org/10.1016/S0024-3205(00)00470-7] [PMID: 10794500] 
[371] 
Ahmad J, Akhter S, Rizwanullah M, et al. Nanotechnology Based Theranostic Approaches in Alzheimer’s Disease Management: Current Status and Future Perspective. Curr Alzheimer Res  2017; 14(11): 1164-81.
[http://dx.doi.org/10.2174/1567205014666170508121031] [PMID: 28482786] 
[372] 
Zhou X, Xi W, Luo Y, Cao S, Wei G. Interactions of a water-soluble fullerene derivative with amyloid-β protofibrils: dynamics, binding mechanism, and the resulting salt-bridge disruption. J Phys Chem B  2014; 118(24): 6733-41.
[http://dx.doi.org/10.1021/jp503458w] [PMID: 24857343] 
[373] 
Cimini A, D’Angelo B, Das S, et al. Antibody-conjugated PEGylated cerium oxide nanoparticles for specific targeting of Aβ aggregates modulate neuronal survival pathways. Acta Biomater  2012; 8(6): 2056-67.
[http://dx.doi.org/10.1016/j.actbio.2012.01.035] [PMID: 22343002] 
[374] 
Stiriba SE, Frey H, Haag R. Dendritic polymers in biomedical applications: from potential to clinical use in diagnostics and therapy. Angew Chem Int Ed Engl  2002; 41(8): 1329-34.
[http://dx.doi.org/10.1002/1521-3773(20020415)41:8<1329::AID-ANIE1329>3.0.CO;2-P] [PMID: 19750755] 
[375] 
Lowe TL, Strzelec A, Kiessling LL, Murphy RM. Structure-function relationships for inhibitors of beta-amyloid toxicity containing the recognition sequence KLVFF. Biochemistry  2001; 40(26): 7882-9.
[http://dx.doi.org/10.1021/bi002734u] [PMID: 11425316] 
[376] 
Chafekar SM, Malda H, Merkx M, et al. Branched KLVFF tetramers strongly potentiate inhibition of beta-amyloid aggregation. ChemBioChem  2007; 8(15): 1857-64.
[http://dx.doi.org/10.1002/cbic.200700338] [PMID: 17763487] 
[377] 
Patel D, Henry J, Good T. Attenuation of beta-amyloid induced toxicity by sialic acid-conjugated dendrimeric polymers. Biochim Biophys Acta  2006; 1760(12): 1802-9.
[http://dx.doi.org/10.1016/j.bbagen.2006.08.008] [PMID: 16982154] 
[378] 
Klajnert B, Cladera J, Bryszewska M. Molecular interactions of dendrimers with amyloid peptides: pH dependence. Biomacromolecules  2006; 7(7): 2186-91.
[http://dx.doi.org/10.1021/bm060229s] [PMID: 16827586] 
[379] 
Ciepluch K, Weber M, Katir N, et al. Effect of viologen-phosphorus dendrimers on acetylcholinesterase and butyrylcholinesterase activities. Int J Biol Macromol  2013; 54: 119-24.
[http://dx.doi.org/10.1016/j.ijbiomac.2012.12.002] [PMID: 23237795] 
[380] 
Wasiak T, Ionov M, Nieznanski K, et al. Phosphorus dendrimers affect Alzheimer’s (Aβ1-28) peptide and MAP-Tau protein aggregation. Mol Pharm  2012; 9(3): 458-69.
[http://dx.doi.org/10.1021/mp2005627] [PMID: 22206488] 
[381] 
Kogan MJ, Bastus NG, Amigo R, et al. Nanoparticle-mediated local and remote manipulation of protein aggregation. Nano Lett  2006; 6(1): 110-5.
[http://dx.doi.org/10.1021/nl0516862] [PMID: 16402797] 
[382] 
Liao YH, Chang YJ, Yoshiike Y, Chang YC, Chen YR. Negatively charged gold nanoparticles inhibit Alzheimer’s amyloid-β fibrillization, induce fibril dissociation, and mitigate neurotoxicity. Small  2012; 8(23): 3631-9.
[http://dx.doi.org/10.1002/smll.201201068] [PMID: 22915547] 
[383] 
Prades R, Guerrero S, Araya E, et al. Delivery of gold nanoparticles to the brain by conjugation with a peptide that recognizes the transferrin receptor. Biomaterials  2012; 33(29): 7194-205.
[http://dx.doi.org/10.1016/j.biomaterials.2012.06.063] [PMID: 22795856] 
[384] 
Lipton SA. Paradigm shift in NMDA receptor antagonist drug development: molecular mechanism of uncompetitive inhibition by memantine in the treatment of Alzheimer’s disease and other neurologic disorders. J Alzheimers Dis  2004; 6(6)(Suppl.): S61-74.
[PMID: 15665416] 
[385] 
Sozio P, Cerasa LS, Laserra S, et al. Memantine-sulfur containing antioxidant conjugates as potential prodrugs to improve the treatment of Alzheimer’s disease. Eur J Pharm Sci  2013; 49(2): 187-98.
[http://dx.doi.org/10.1016/j.ejps.2013.02.013] [PMID: 23454012] 
[386] 
Gauthier S, Molinuevo JL. Benefits of combined cholinesterase inhibitor and memantine treatment in moderate-severe Alzheimer’s disease. Alzheimers Dement  2013; 9(3): 326-31.
[http://dx.doi.org/10.1016/j.jalz.2011.11.005] [PMID: 23110864] 
[387] 
Wong HL, Wu XY, Bendayan R. Nanotechnological advances for the delivery of CNS therapeutics. Adv Drug Deliv Rev  2012; 64(7): 686-700.
[http://dx.doi.org/10.1016/j.addr.2011.10.007] [PMID: 22100125] 
[388] 
Brambilla D, Le Droumaguet B, Nicolas J, et al. Nanotechnologies for Alzheimer’s disease: diagnosis, therapy, and safety issues. Nanomedicine (Lond)  2011; 7(5): 521-40.
[http://dx.doi.org/10.1016/j.nano.2011.03.008] [PMID: 21477665] 
[389] 
Ahmad MZ, Akhter S, Mohsin N, et al. Transformation of curcumin from food additive to multifunctional medicine: nanotechnology bridging the gap. Curr Drug Discov Technol  2014; 11(3): 197-213.
[http://dx.doi.org/10.2174/1570163811666140616153436] [PMID: 24934264] 
[390] 
Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL. A potential role of the curry spice curcumin in Alzheimer’s disease. Curr Alzheimer Res  2005; 2(2): 131-6.
[http://dx.doi.org/10.2174/1567205053585882] [PMID: 15974909] 
[391] 
Tandon A, Singh S J, Chaturvedi R K. Stem Cells as Potential Targets of Polyphenols in Multiple Sclerosis and Alzheimer's Disease. Biomed Res Int 2018.
[392] 
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm  2007; 4(6): 807-18.
[http://dx.doi.org/10.1021/mp700113r] [PMID: 17999464] 
[393] 
Barbara R, Belletti D, Pederzoli F, et al. Novel Curcumin loaded nanoparticles engineered for Blood-Brain Barrier crossing and able to disrupt Abeta aggregates. Int J Pharm  2017; 526(1-2): 413-24.
[http://dx.doi.org/10.1016/j.ijpharm.2017.05.015] [PMID: 28495580] 
[394] 
Mulik RS, Mönkkönen J, Juvonen RO, Mahadik KR, Paradkar AR. ApoE3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin: study of enhanced activity of curcumin against beta amyloid induced cytotoxicity using in vitro cell culture model. Mol Pharm  2010; 7(3): 815-25.
[http://dx.doi.org/10.1021/mp900306x] [PMID: 20230014] 
[395] 
Doggui S, Sahni JK, Arseneault M, Dao L, Ramassamy C. Neuronal uptake and neuroprotective effect of curcumin-loaded PLGA nanoparticles on the human SK-N-SH cell line. J Alzheimers Dis  2012; 30(2): 377-92.
[http://dx.doi.org/10.3233/JAD-2012-112141] [PMID: 22426019] 
[396] 
Mathew A, Fukuda T, Nagaoka Y, et al. Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer’s disease. PLoS One  2012; 7(3): e32616.
[http://dx.doi.org/10.1371/journal.pone.0032616] [PMID: 22403681] 
[397] 
Lazar AN, Mourtas S, Youssef I, et al. Curcumin-conjugated nanoliposomes with high affinity for Aβ deposits: possible applications to Alzheimer disease. Nanomedicine (Lond)  2013; 9(5): 712-21.
[http://dx.doi.org/10.1016/j.nano.2012.11.004] [PMID: 23220328] 
[398] 
Cheng KK, Yeung CF, Ho SW, Chow SF, Chow AH, Baum L. Highly stabilized curcumin nanoparticles tested in an in vitro blood-brain barrier model and in Alzheimer’s disease Tg2576 mice. AAPS J  2013; 15(2): 324-36.
[http://dx.doi.org/10.1208/s12248-012-9444-4] [PMID: 23229335] 
[399] 
Sinha A, Tamboli R S, Seth B, et al. Neuroprotective Role of Novel Triazine Derivatives by Activating Wnt/beta Catenin Signaling Pathway in Rodent Models of Alzheimer's Disease. Mol Neurobiol  2015; 52: 638-52.
[400] 
Tiwari SK, Agarwal S, Seth B, et al. Inhibitory Effects of Bisphenol-A on Neural Stem Cells Proliferation and Differentiation in the Rat Brain Are Dependent on Wnt/β-Catenin Pathway. Mol Neurobiol  2015; 52(3): 1735-57.
[http://dx.doi.org/10.1007/s12035-014-8940-1] [PMID: 25381574] 
[401] 
Tiwari SK, Agarwal S, Tripathi A, Chaturvedi RK. Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway. Mol Neurobiol  2016; 53(5): 3010-29.
[http://dx.doi.org/10.1007/s12035-015-9197-z] [PMID: 25963729] 
[402] 
Tiwari SK, Seth B, Agarwal S, et al. Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-β Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/β-Catenin Pathway. J Biol Chem  2015; 290(47): 28540-58.
[http://dx.doi.org/10.1074/jbc.M115.652586] [PMID: 26420483] 
[403] 
Tiwari SK, Agarwal S, Seth B, et al. Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer’s disease model via canonical Wnt/β-catenin pathway. ACS Nano  2014; 8(1): 76-103.
[http://dx.doi.org/10.1021/nn405077y] [PMID: 24467380] 
[404] 
Gauthier S, Juby A, Dalziel W, Réhel B, Schecter R. EXPLORE investigators. Effects of rivastigmine on common symptomatology of Alzheimer’s disease (EXPLORE). Curr Med Res Opin  2010; 26(5): 1149-60.
[http://dx.doi.org/10.1185/03007991003688888] [PMID: 20230208] 
[405] 
Wilson B, Samanta MK, Santhi K, Kumar KP, Paramakrishnan N, Suresh B. Poly(n-butylcyanoacrylate) nanoparticles coated with polysorbate 80 for the targeted delivery of rivastigmine into the brain to treat Alzheimer’s disease. Brain Res  2008; 1200: 159-68.
[http://dx.doi.org/10.1016/j.brainres.2008.01.039] [PMID: 18291351] 
[406] 
Wilson B, Samanta MK, Santhi K, Kumar KP, Paramakrishnan N, Suresh B. Targeted delivery of tacrine into the brain with polysorbate 80-coated poly(n-butylcyanoacrylate) nanoparticles. Eur J Pharm Biopharm  2008; 70(1): 75-84.
[http://dx.doi.org/10.1016/j.ejpb.2008.03.009] [PMID: 18472255] 
[407] 
Joshi SA, Chavhan SS, Sawant KK. Rivastigmine-loaded PLGA and PBCA nanoparticles: preparation, optimization, characterization, in vitro and pharmacodynamic studies. Eur J Pharm Biopharm  2010; 76(2): 189-99.
[http://dx.doi.org/10.1016/j.ejpb.2010.07.007] [PMID: 20637869] 
[408] 
Wavikar PR, Vavia PR. Rivastigmine-loaded in situ gelling nanostructured lipid carriers for nose to brain delivery. J Liposome Res  2015; 25(2): 141-9.
[http://dx.doi.org/10.3109/08982104.2014.954129] [PMID: 25203610] 
[409] 
Li W, Zhou Y, Zhao N, Hao B, Wang X, Kong P. Pharmacokinetic behavior and efficiency of acetylcholinesterase inhibition in rat brain after intranasal administration of galanthamine hydrobromide loaded flexible liposomes. Environ Toxicol Pharmacol  2012; 34(2): 272-9.
[http://dx.doi.org/10.1016/j.etap.2012.04.012] [PMID: 22613079] 
[410] 
Pike CJ, Carroll JC, Rosario ER, Barron AM. Protective actions of sex steroid hormones in Alzheimer’s disease. Front Neuroendocrinol  2009; 30(2): 239-58.
[http://dx.doi.org/10.1016/j.yfrne.2009.04.015] [PMID: 19427328] 
[411] 
Amtul Z, Wang L, Westaway D, Rozmahel RF. Neuroprotective mechanism conferred by 17beta-estradiol on the biochemical basis of Alzheimer’s disease. Neuroscience  2010; 169(2): 781-6.
[http://dx.doi.org/10.1016/j.neuroscience.2010.05.031] [PMID: 20493928] 
[412] 
Mittal G, Sahana DK, Bhardwaj V, Ravi Kumar MN. Estradiol loaded PLGA nanoparticles for oral administration: effect of polymer molecular weight and copolymer composition on release behavior in vitro and in vivo. J Control Release  2007; 119(1): 77-85.
[http://dx.doi.org/10.1016/j.jconrel.2007.01.016] [PMID: 17349712] 
[413] 
Lam FC, Liu R, Lu P, et al. beta-Amyloid efflux mediated by p-glycoprotein. J Neurochem  2001; 76(4): 1121-8.
[http://dx.doi.org/10.1046/j.1471-4159.2001.00113.x] [PMID: 11181832] 
[414] 
He W, Horn SW, Hussain MD. Improved bioavailability of orally administered mifepristone from PLGA nanoparticles. Int J Pharm  2007; 334(1-2): 173-8.
[http://dx.doi.org/10.1016/j.ijpharm.2006.10.025] [PMID: 17101249] 
[415] 
Mittal G, Carswell H, Brett R, Currie S, Kumar MN. Development and evaluation of polymer nanoparticles for oral delivery of estradiol to rat brain in a model of Alzheimer’s pathology. J Control Release  2011; 150(2): 220-8.
[http://dx.doi.org/10.1016/j.jconrel.2010.11.013] [PMID: 21111014] 
[416] 
Rezai-Zadeh K, Arendash GW, Hou H, et al. Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res  2008; 1214: 177-87.
[http://dx.doi.org/10.1016/j.brainres.2008.02.107] [PMID: 18457818] 
[417] 
Vassar R. Beta-secretase (BACE) as a drug target for Alzheimer’s disease. Adv Drug Deliv Rev  2002; 54(12): 1589-602.
[http://dx.doi.org/10.1016/S0169-409X(02)00157-6] [PMID: 12453676] 
[418] 
Smith A, Giunta B, Bickford PC, Fountain M, Tan J, Shytle RD. Nanolipidic particles improve the bioavailability and alpha-secretase inducing ability of epigallocatechin-3-gallate (EGCG) for the treatment of Alzheimer’s disease. Int J Pharm  2010; 389(1-2): 207-12.
[http://dx.doi.org/10.1016/j.ijpharm.2010.01.012] [PMID: 20083179] 
[419] 
Zhang J, Zhou X, Yu Q, et al. Epigallocatechin-3-gallate (EGCG)-stabilized selenium nanoparticles coated with Tet-1 peptide to reduce amyloid-β aggregation and cytotoxicity. ACS Appl Mater Interfaces  2014; 6(11): 8475-87.
[http://dx.doi.org/10.1021/am501341u] [PMID: 24758520] 
[420] 
Ahmad MZ, Ahmad J, Amin S, et al. Role of nanomedicines in delivery of anti-acetylcholinesterase compounds to the brain in Alzheimer’s disease. CNS Neurol Disord Drug Targets  2014; 13(8): 1315-24.
[http://dx.doi.org/10.2174/1871527313666141023100618] [PMID: 25345516] 
[421] 
Pangeni R, Sahni JK, Ali J, Sharma S, Baboota S. Resveratrol: review on therapeutic potential and recent advances in drug delivery. Expert Opin Drug Deliv  2014; 11(8): 1285-98.
[http://dx.doi.org/10.1517/17425247.2014.919253] [PMID: 24830814] 
[422] 
Kim YA, Lim SY, Rhee SH, et al. Resveratrol inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression in beta-amyloid-treated C6 glioma cells. Int J Mol Med  2006; 17(6): 1069-75.
[PMID: 16685418] 
[423] 
Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimer’s disease amyloid-beta peptides. J Biol Chem  2005; 280(45): 37377-82.
[http://dx.doi.org/10.1074/jbc.M508246200] [PMID: 16162502] 
[424] 
Frozza RL, Bernardi A, Hoppe JB, et al. Neuroprotective effects of resveratrol against Aβ administration in rats are improved by lipid-core nanocapsules. Mol Neurobiol  2013; 47(3): 1066-80.
[http://dx.doi.org/10.1007/s12035-013-8401-2] [PMID: 23315270] 
[425] 
da Rocha Lindner G, Khalil NM, Mainardes RM. Resveratrol-loaded polymeric nanoparticles: validation of an HPLC-PDA method to determine the drug entrapment and evaluation of its antioxidant activity. ScientificWorldJournal  2013; 2013: 506083.
[http://dx.doi.org/10.1155/2013/506083] [PMID: 24282384] 
[426] 
Bush AI. Drug development based on the metals hypothesis of Alzheimer’s disease. J Alzheimers Dis  2008; 15(2): 223-40.
[http://dx.doi.org/10.3233/JAD-2008-15208] [PMID: 18953111] 
[427] 
Curtain CC, Ali F, Volitakis I, et al. Alzheimer’s disease amyloid-beta binds copper and zinc to generate an allosterically ordered membrane-penetrating structure containing superoxide dismutase-like subunits. J Biol Chem  2001; 276(23): 20466-73.
[http://dx.doi.org/10.1074/jbc.M100175200] [PMID: 11274207] 
[428] 
Liu G, Men P, Harris PL, Rolston RK, Perry G, Smith MA. Nanoparticle iron chelators: a new therapeutic approach in Alzheimer disease and other neurologic disorders associated with trace metal imbalance. Neurosci Lett  2006; 406(3): 189-93.
[http://dx.doi.org/10.1016/j.neulet.2006.07.020] [PMID: 16919875] 
[429] 
Liu G, Men P, Kudo W, Perry G, Smith MA. Nanoparticle-chelator conjugates as inhibitors of amyloid-beta aggregation and neurotoxicity: a novel therapeutic approach for Alzheimer disease. Neurosci Lett  2009; 455(3): 187-90.
[http://dx.doi.org/10.1016/j.neulet.2009.03.064] [PMID: 19429118] 
[430] 
Cui Z, Lockman PR, Atwood CS, et al. Novel D-penicillamine carrying nanoparticles for metal chelation therapy in Alzheimer’s and other CNS diseases. Eur J Pharm Biopharm  2005; 59(2): 263-72.
[http://dx.doi.org/10.1016/j.ejpb.2004.07.009] [PMID: 15661498] 
[431] 
Ritchie CW, Bush AI, Mackinnon A, et al. Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Arch Neurol  2003; 60(12): 1685-91.
[http://dx.doi.org/10.1001/archneur.60.12.1685] [PMID: 14676042] 
[432] 
Cherny RA, Atwood CS, Xilinas ME, et al. Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer’s disease transgenic mice. Neuron  2001; 30(3): 665-76.
[http://dx.doi.org/10.1016/S0896-6273(01)00317-8] [PMID: 11430801] 
[433] 
Mufamadi MS, Choonara YE, Kumar P, et al. Surface-engineered nanoliposomes by chelating ligands for modulating the neurotoxicity associated with β-amyloid aggregates of Alzheimer’s disease. Pharm Res  2012; 29(11): 3075-89.
[http://dx.doi.org/10.1007/s11095-012-0770-0] [PMID: 22584945] 
[434] 
Singh N, Pillay V, Choonara YE. Advances in the treatment of Parkinson’s disease. Prog Neurobiol  2007; 81(1): 29-44.
[http://dx.doi.org/10.1016/j.pneurobio.2006.11.009] [PMID: 17258379] 
[435] 
Modi G, Pillay V, Choonara YE, Ndesendo VM, du Toit LC, Naidoo D. Nanotechnological applications for the treatment of neurodegenerative disorders. Prog Neurobiol  2009; 88(4): 272-85.
[http://dx.doi.org/10.1016/j.pneurobio.2009.05.002] [PMID: 19486920] 
[436] 
Malvindi MA, Di Corato R, Curcio A, et al. Multiple functionalization of fluorescent nanoparticles for specific biolabeling and drug delivery of dopamine. Nanoscale  2011; 3(12): 5110-9.
[http://dx.doi.org/10.1039/c1nr10797f] [PMID: 22037807] 
[437] 
Linazasoro G. Nanotechnologies for Neurodegenerative Diseases Study Group of the Basque Country (NANEDIS). Potential applications of nanotechnologies to Parkinson’s disease therapy. Parkinsonism Relat Disord  2008; 14(5): 383-92.
[http://dx.doi.org/10.1016/j.parkreldis.2007.11.012] [PMID: 18329315] 
[438] 
Ngwuluka NC, Pillay V, Choonara YE, et al. Fabrication, modeling and characterization of multi-crosslinked methacrylate copolymeric nanoparticles for oral drug delivery. Int J Mol Sci  2011; 12(9): 6194-225.
[http://dx.doi.org/10.3390/ijms12096194] [PMID: 22016653] 
[439] 
Sadigh-Eteghad S, Talebi M, Farhoudi M, Mahmoudi J, Reyhani B. Effects of Levodopa loaded chitosan nanoparticles on cell viability and caspase-3 expression in PC12 neural like cells. Neurosciences (Riyadh)  2013; 18(3): 281-3.
[PMID: 23887222] 
[440] 
Sharma S, Lohan S, Murthy RS. Formulation and characterization of intranasal mucoadhesive nanoparticulates and thermo-reversible gel of levodopa for brain delivery. Drug Dev Ind Pharm  2014; 40(7): 869-78.
[http://dx.doi.org/10.3109/03639045.2013.789051] [PMID: 23600649] 
[441] 
Yang X, Zheng R, Cai Y, Liao M, Yuan W, Liu Z. Controlled-release levodopa methyl ester/benserazide-loaded nanoparticles ameliorate levodopa-induced dyskinesia in rats. Int J Nanomedicine  2012; 7: 2077-86.
[PMID: 22619544] 
[442] 
Re F, Gregori M, Masserini M. Nanotechnology for neurodegenerative disorders. Maturitas  2012; 73(1): 45-51.
[http://dx.doi.org/10.1016/j.maturitas.2011.12.015] [PMID: 22261367] 
[443] 
Mohanraj K, Sethuraman S, Krishnan UM. Development of poly(butylene succinate) microspheres for delivery of levodopa in the treatment of Parkinson’s disease. J Biomed Mater Res B Appl Biomater  2013; 101(5): 840-7.
[http://dx.doi.org/10.1002/jbm.b.32888] [PMID: 23401377] 
[444] 
Trapani A, De Giglio E, Cafagna D, et al. Characterization and evaluation of chitosan nanoparticles for dopamine brain delivery. Int J Pharm  2011; 419(1-2): 296-307.
[http://dx.doi.org/10.1016/j.ijpharm.2011.07.036] [PMID: 21821107] 
[445] 
Pillay S, Pillay V, Choonara YE, et al. Design, biometric simulation and optimization of a nano-enabled scaffold device for enhanced delivery of dopamine to the brain. Int J Pharm  2009; 382(1-2): 277-90.
[http://dx.doi.org/10.1016/j.ijpharm.2009.08.021] [PMID: 19703530] 
[446] 
Gambaryan PY, Kondrasheva IG, Severin ES, Guseva AA, Kamensky AA. Increasing the Efficiency of Parkinson’s Disease Treatment Using a poly(lactic-co-glycolic acid) (PLGA) Based L-DOPA Delivery System. Exp Neurobiol  2014; 23(3): 246-52.
[http://dx.doi.org/10.5607/en.2014.23.3.246] [PMID: 25258572] 
[447] 
Leyva-Gómez G, Cortés H, Magaña JJ, Leyva-García N, Quintanar-Guerrero D, Florán B. Nanoparticle technology for treatment of Parkinson’s disease: the role of surface phenomena in reaching the brain. Drug Discov Today  2015; 20(7): 824-37.
[http://dx.doi.org/10.1016/j.drudis.2015.02.009] [PMID: 25701281] 
[448] 
Pahuja R, Seth K, Shukla A, et al. Trans-blood brain barrier delivery of dopamine-loaded nanoparticles reverses functional deficits in parkinsonian rats. ACS Nano  2015; 9(5): 4850-71.
[http://dx.doi.org/10.1021/nn506408v] [PMID: 25825926] 
[449] 
Esposito E, Mariani P, Ravani L, et al. Nanoparticulate lipid dispersions for bromocriptine delivery: characterization and in vivo study. Eur J Pharm Biopharm  2012; 80(2): 306-14.
[http://dx.doi.org/10.1016/j.ejpb.2011.10.015] [PMID: 22061262] 
[450] 
Wen CJ, Zhang LW, Al-Suwayeh SA, Yen TC, Fang JY. Theranostic liposomes loaded with quantum dots and apomorphine for brain targeting and bioimaging. Int J Nanomedicine  2012; 7: 1599-611.
[PMID: 22619515] 
[451] 
Hsu SH, Wen CJ, Al-Suwayeh SA, Chang HW, Yen TC, Fang JY. Physicochemical characterization and in vivo bioluminescence imaging of nanostructured lipid carriers for targeting the brain: apomorphine as a model drug. Nanotechnology  2010; 21(40): 405101.
[http://dx.doi.org/10.1088/0957-4484/21/40/405101] [PMID: 20823498] 
[452] 
Pardeshi CV, Belgamwar VS, Tekade AR, Surana SJ. Novel surface modified polymer-lipid hybrid nanoparticles as intranasal carriers for ropinirole hydrochloride: in vitro, ex vivo and in vivo pharmacodynamic evaluation. J Mater Sci Mater Med  2013; 24(9): 2101-15.
[http://dx.doi.org/10.1007/s10856-013-4965-7] [PMID: 23728521] 
[453] 
Yoo J, Lee E, Kim HY, et al. Electromagnetized gold nanoparticles mediate direct lineage reprogramming into induced dopamine neurons in vivo for Parkinson’s disease therapy. Nat Nanotechnol  2017; 12(10): 1006-14.
[http://dx.doi.org/10.1038/nnano.2017.133] [PMID: 28737745] 
[454] 
Tavakol S, Musavi SMM, Tavakol B, Hoveizi E, Ai J, Rezayat SM. Erratum to: Noggin Along with a Self-Assembling Peptide Nanofiber Containing Long Motif of Laminin Induces Tyrosine Hydroxylase Gene Expression. Mol Neurobiol  2017; 54(6): 4617.
[http://dx.doi.org/10.1007/s12035-016-0069-y] [PMID: 27578010] 
[455] 
Raj MA, Gowthaman NS, John SA. Highly sensitive interference-free electrochemical determination of pyridoxine at graphene modified electrode: Importance in Parkinson and Asthma treatments. J Colloid Interface Sci  2016; 474: 171-8.
[http://dx.doi.org/10.1016/j.jcis.2016.04.025] [PMID: 27124811] 
[456] 
Miklya I. [The feasibility of synthetic enhancer substances for preventive nanotherapy]. Neuropsychopharmacol Hung  2010; 12(3): 395-403. [The feasibility of synthetic enhancer substances for preventive nanotherapy].
[PMID: 20962359] 
[457] 
Haney MJ, Klyachko NL, Zhao Y, et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release  2015; 207: 18-30.
[http://dx.doi.org/10.1016/j.jconrel.2015.03.033] [PMID: 25836593] 
[458] 
Nanjwade BK, Kadam VT, Manvi FV. Formulation and characterization of nanostructured lipid carrier of ubiquinone (Coenzyme Q10). J Biomed Nanotechnol  2013; 9(3): 450-60.
[http://dx.doi.org/10.1166/jbn.2013.1560] [PMID: 23621001] 
[459] 
Swarnakar NK, Jain AK, Singh RP, Godugu C, Das M, Jain S. Oral bioavailability, therapeutic efficacy and reactive oxygen species scavenging properties of coenzyme Q10-loaded polymeric nanoparticles. Biomaterials  2011; 32(28): 6860-74.
[http://dx.doi.org/10.1016/j.biomaterials.2011.05.079] [PMID: 21704368] 
[460] 
Zhao Y, Haney MJ, Gupta R, et al. GDNF-transfected macrophages produce potent neuroprotective effects in Parkinson’s disease mouse model. PLoS One  2014; 9(9): e106867.
[http://dx.doi.org/10.1371/journal.pone.0106867] [PMID: 25229627] 
[461] 
Singhal A, Morris VB, Labhasetwar V, Ghorpade A. Nanoparticle-mediated catalase delivery protects human neurons from oxidative stress. Cell Death Dis  2013; 4: e903.
[http://dx.doi.org/10.1038/cddis.2013.362] [PMID: 24201802] 
[462] 
Pangeni R, Sharma S, Mustafa G, Ali J, Baboota S. Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson’s disease by reducing oxidative stress. Nanotechnology  2014; 25(48): 485102.
[http://dx.doi.org/10.1088/0957-4484/25/48/485102] [PMID: 25392203] 
[463] 
Mazza M, Notman R, Anwar J, et al. Nanofiber-based delivery of therapeutic peptides to the brain. ACS Nano  2013; 7(2): 1016-26.
[http://dx.doi.org/10.1021/nn305193d] [PMID: 23289352] 
[464] 
Nagpal K, Singh SK, Mishra DN. Optimization of brain targeted chitosan nanoparticles of Rivastigmine for improved efficacy and safety. Int J Biol Macromol  2013; 59: 72-83.
[http://dx.doi.org/10.1016/j.ijbiomac.2013.04.024] [PMID: 23597710] 
[465] 
Tiwari SK, Chaturvedi RK. Peptide therapeutics in neurodegenerative disorders. Curr Med Chem  2014; 21(23): 2610-31.
[http://dx.doi.org/10.2174/0929867321666140217125857] [PMID: 24533803] 
[466] 
Samal J, Hoban DB, Naughton C, Concannon R, Dowd E, Pandit A. Fibrin-based microsphere reservoirs for delivery of neurotrophic factors to the brain. Nanomedicine (Lond)  2015; 10(5): 765-83.
[http://dx.doi.org/10.2217/nnm.14.221] [PMID: 25816879] 
[467] 
Chiu S, Terpstra KJ, Bureau Y, et al. Liposomal-formulated curcumin [Lipocurc™] targeting HDAC (histone deacetylase) prevents apoptosis and improves motor deficits in Park 7 (DJ-1)-knockout rat model of Parkinson’s disease: implications for epigenetics-based nanotechnology-driven drug platform. J Complement Integr Med  2013; 10: 10.
[http://dx.doi.org/10.1515/jcim-2013-0020] [PMID: 24200537] 
[468] 
Hernandez ME, Rembao JD, Hernandez-Baltazar D, et al. Safety of the intravenous administration of neurotensin-polyplex nanoparticles in BALB/c mice. Nanomedicine (Lond)  2014; 10(4): 745-54.
[http://dx.doi.org/10.1016/j.nano.2013.11.013] [PMID: 24333586] 
[469] 
Corso TD, Torres G, Goulah C, et al. Assessment of viral and non-viral gene transfer into adult rat brains using HSV-1, calcium phosphate and PEI-based methods. Folia Morphol (Warsz)  2005; 64(3): 130-44.
[PMID: 16228947] 
[470] 
Yue K, Guduru R, Hong J, Liang P, Nair M, Khizroev S. Magneto-electric nano-particles for non-invasive brain stimulation. PLoS One  2012; 7(9): e44040.
[http://dx.doi.org/10.1371/journal.pone.0044040] [PMID: 22957042] 
[471] 
Tiwari MN, Agarwal S, Bhatnagar P, et al. Nicotine-encapsulated poly(lactic-co-glycolic) acid nanoparticles improve neuroprotective efficacy against MPTP-induced parkinsonism. Free Radic Biol Med  2013; 65: 704-18.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.07.042] [PMID: 23933227] 
[472] 
Singhal NK, Agarwal S, Bhatnagar P, et al. Mechanism of Nanotization-Mediated Improvement in the Efficacy of Caffeine Against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinsonism. J Biomed Nanotechnol  2015; 11(12): 2211-22.
[http://dx.doi.org/10.1166/jbn.2015.2107] [PMID: 26510314] 
[473] 
Hu K, Shi Y, Jiang W, Han J, Huang S, Jiang X. Lactoferrin conjugated PEG-PLGA nanoparticles for brain delivery: preparation, characterization and efficacy in Parkinson’s disease. Int J Pharm  2011; 415(1-2): 273-83.
[http://dx.doi.org/10.1016/j.ijpharm.2011.05.062] [PMID: 21651967] 
[474] 
Wen Z, Yan Z, Hu K, et al. Odorranalectin-conjugated nanoparticles: preparation, brain delivery and pharmacodynamic study on Parkinson’s disease following intranasal administration. J Control Release  2011; 151(2): 131-8.
[http://dx.doi.org/10.1016/j.jconrel.2011.02.022] [PMID: 21362449] 
[475] 
Muthu MS, Singh S. Studies on biodegradable polymeric nanoparticles of risperidone: in vitro and in vivo evaluation. Nanomedicine (Lond)  2008; 3(3): 305-19.
[http://dx.doi.org/10.2217/17435889.3.3.305] [PMID: 18510426] 
[476] 
Muthu MS, Rawat MK, Mishra A, Singh S. PLGA nanoparticle formulations of risperidone: preparation and neuropharmacological evaluation. Nanomedicine (Lond)  2009; 5(3): 323-33.
[http://dx.doi.org/10.1016/j.nano.2008.12.003] [PMID: 19523427] 
[477] 
Cai X, Zhang K, Xie X, et al. Self-assembly hollow manganese Prussian white nanocapsules attenuate Tau-related neuropathology and cognitive decline. Biomaterials  2020; 231: 119678.
[http://dx.doi.org/10.1016/j.biomaterials.2019.119678] [PMID: 31864019] 
[478] 
Pederzoli F, Ruozi B, Duskey J, et al. Nanomedicine Against Abeta Aggregation by beta-Sheet Breaker Peptide Delivery: In Vitro Evidence. Pharmaceutics  2019; 11.
[479] 
Zhao Y, Cai J, Liu Z, et al. Nanocomposites Inhibit the Formation, Mitigate the Neurotoxicity, and Facilitate the Removal of β-Amyloid Aggregates in Alzheimer’s Disease Mice. Nano Lett  2019; 19(2): 674-83.
[http://dx.doi.org/10.1021/acs.nanolett.8b03644] [PMID: 30444372] 
[480] 
Javed I, Peng G, Xing Y, et al. Inhibition of amyloid beta toxicity in zebrafish with a chaperone-gold nanoparticle dual strategy. Nat Commun  2019; 10(1): 3780.
[http://dx.doi.org/10.1038/s41467-019-11762-0] [PMID: 31439844] 
[481] 
Katebi S, Esmaeili A, Ghaedi K, Zarrabi A. Superparamagnetic iron oxide nanoparticles combined with NGF and quercetin promote neuronal branching morphogenesis of PC12 cells. Int J Nanomedicine  2019; 14: 2157-69.
[http://dx.doi.org/10.2147/IJN.S191878] [PMID: 30992663] 
[482] 
Jeon SG, Cha MY, Kim JI, et al. Vitamin D-binding protein-loaded PLGA nanoparticles suppress Alzheimer’s disease-related pathology in 5XFAD mice. Nanomedicine (Lond)  2019; 17: 297-307.
[http://dx.doi.org/10.1016/j.nano.2019.02.004] [PMID: 30794963] 
[483] 
Aso E, Martinsson I, Appelhans D, et al. Poly(propylene imine) dendrimers with histidine-maltose shell as novel type of nanoparticles for synapse and memory protection. Nanomedicine (Lond)  2019; 17: 198-209.
[http://dx.doi.org/10.1016/j.nano.2019.01.010] [PMID: 30708052] 
[484] 
Zhang L, Zhao P, Yue C, et al. Sustained release of bioactive hydrogen by Pd hydride nanoparticles overcomes Alzheimer’s disease. Biomaterials  2019; 197: 393-404.
[http://dx.doi.org/10.1016/j.biomaterials.2019.01.037] [PMID: 30703744] 
[485] 
Zhang H, Zhao Y, Yu M, et al. Reassembly of native components with donepezil to execute dual-missions in Alzheimer’s disease therapy. J Control Release  2019; 296: 14-28.
[http://dx.doi.org/10.1016/j.jconrel.2019.01.008] [PMID: 30639387] 
[486] 
Sunena SK, Singh SK, Mishra DN. Nose to brain delivery of galantamine loaded nanoparticles: In-vivo pharmacodynamic and biochemical study in mice. Curr Drug Deliv  2019; 16(1): 51-8.
[http://dx.doi.org/10.2174/1567201815666181004094707] [PMID: 30289074] 
[487] 
Huo X, Zhang Y, Jin X, Li Y, Zhang L. A novel synthesis of selenium nanoparticles encapsulated PLGA nanospheres with curcumin molecules for the inhibition of amyloid β aggregation in Alzheimer’s disease. J Photochem Photobiol B  2019; 190: 98-102.
[http://dx.doi.org/10.1016/j.jphotobiol.2018.11.008] [PMID: 30504054] 
[488] 
Mirzaie Z, Ansari M, Kordestani SS, Rezaei MH, Mozafari M. Preparation and characterization of curcumin-loaded polymeric nanomicelles to interference with amyloidogenesis through glycation method. Biotechnol Appl Biochem  2019; 66(4): 537-44.
[http://dx.doi.org/10.1002/bab.1751] [PMID: 30993734] 
[489] 
Park H, Oh J, Shim G, et al. In vivo neuronal gene editing via CRISPR-Cas9 amphiphilic nanocomplexes alleviates deficits in mouse models of Alzheimer’s disease. Nat Neurosci  2019; 22(4): 524-8.
[http://dx.doi.org/10.1038/s41593-019-0352-0] [PMID: 30858603] 
[490] 
Cano A, Ettcheto M, Chang JH, et al. Dual-drug loaded nanoparticles of Epigallocatechin-3-gallate (EGCG)/Ascorbic acid enhance therapeutic efficacy of EGCG in a APPswe/PS1dE9 Alzheimer’s disease mice model. J Control Release  2019; 301: 62-75.
[http://dx.doi.org/10.1016/j.jconrel.2019.03.010] [PMID: 30876953] 
[491] 
Nday C M, Eleftheriadou D, Jackson G. Naringin nanoparticles against neurodegenerative processes: A preliminary work. Hell J Nucl Med  2019; 22: 32-41.
[492] 
Nday C M, Eleftheriadou D, Jackson G. Magnetic chrysin silica nanomaterials behavior in an amyloidogenic environment. Hell J Nucl Med  2019; 22: 42-50.
[493] 
Liu Y, Zhou H, Yin T, et al. Quercetin-modified gold-palladium nanoparticles as a potential autophagy inducer for the treatment of Alzheimer’s disease. J Colloid Interface Sci  2019; 552: 388-400.
[http://dx.doi.org/10.1016/j.jcis.2019.05.066] [PMID: 31151017] 
[494] 
Chung YJ, Lee BI, Park CB. Multifunctional carbon dots as a therapeutic nanoagent for modulating Cu(ii)-mediated β-amyloid aggregation. Nanoscale  2019; 11(13): 6297-306.
[http://dx.doi.org/10.1039/C9NR00473D] [PMID: 30882825] 
[495] 
Kim D, Kwon H J, Hyeon T. Magnetite/Ceria Nanoparticle Assemblies for Extracorporeal Cleansing of Amyloid-beta in Alzheimer's Disease. Adv Mater 2019.
[496] 
Dos Santos Rodrigues B, Kanekiyo T, Singh J. ApoE-2 brain-targeted gene therapy through transferrin and penetratin tagged liposomal nanoparticles. Pharm Res  2019; 36(11): 161.
[http://dx.doi.org/10.1007/s11095-019-2691-7] [PMID: 31529284] 
[497] 
Youssif KA, Haggag EG, Elshamy AM, et al. Anti-Alzheimer potential, metabolomic profiling and molecular docking of green synthesized silver nanoparticles of Lampranthus coccineus and Malephora lutea aqueous extracts. PLoS One  2019; 14(11): e0223781.
[http://dx.doi.org/10.1371/journal.pone.0223781] [PMID: 31693694] 
[498] 
Sathya S, Shanmuganathan B, Balasubramaniam B, Balamurugan K, Devi KP. Phytol loaded PLGA nanoparticles regulate the expression of Alzheimer’s related genes and neuronal apoptosis against amyloid-β induced toxicity in Neuro-2a cells and transgenic Caenorhabditis elegans. Food Chem Toxicol  2020; 136: 110962.
[http://dx.doi.org/10.1016/j.fct.2019.110962] [PMID: 31734340] 
[499] 
Ren C, Li D, Zhou Q, Hu X. Mitochondria-targeted TPP-MoS2 with dual enzyme activity provides efficient neuroprotection through M1/M2 microglial polarization in an Alzheimer’s disease model. Biomaterials  2020; 232: 119752.
[http://dx.doi.org/10.1016/j.biomaterials.2019.119752] [PMID: 31923845] 
[500] 
Negahdary M, Heli H. An electrochemical peptide-based biosensor for the Alzheimer biomarker amyloid-β(1-42) using a microporous gold nanostructure. Mikrochim Acta  2019; 186(12): 766.
[http://dx.doi.org/10.1007/s00604-019-3903-x] [PMID: 31713687] 
[501] 
López-Sanz D, Bruña R, de Frutos-Lucas J, Maestú F. Magnetoencephalography applied to the study of Alzheimer’s disease. Prog Mol Biol Transl Sci  2019; 165: 25-61.
[http://dx.doi.org/10.1016/bs.pmbts.2019.04.007] [PMID: 31481165] 
[502] 
Ni M, Zhuo S, Iliescu C, et al. Self-assembling amyloid-like peptides as exogenous second harmonic probes for bioimaging applications. J Biophotonics  2019; 12(12): e201900065.
[http://dx.doi.org/10.1002/jbio.201900065] [PMID: 31162811] 
[503] 
Negahdary M, Heli H. An ultrasensitive electrochemical aptasensor for early diagnosis of Alzheimer’s disease, using a fern leaves-like gold nanostructure. Talanta  2019; 198: 510-7.
[http://dx.doi.org/10.1016/j.talanta.2019.01.109] [PMID: 30876593] 
[504] 
Tao D, Shui B, Gu Y, et al. Development of a Label-Free Electrochemical Aptasensor for the Detection of Tau381 and its Preliminary Application in AD and Non-AD Patients’ Sera. Biosensors (Basel)  2019; 9(3): 9.
[http://dx.doi.org/10.3390/bios9030084] [PMID: 31262001] 
[505] 
Ahlschwede KM, Curran GL, Rosenberg JT, et al. Cationic carrier peptide enhances cerebrovascular targeting of nanoparticles in Alzheimer’s disease brain. Nanomedicine (Lond)  2019; 16: 258-66.
[http://dx.doi.org/10.1016/j.nano.2018.09.010] [PMID: 30300748] 
[506] 
Han X, Man Z, Xu S, et al. A gold nanocluster chemical tongue sensor array for Alzheimer’s disease diagnosis. Colloids Surf B Biointerfaces  2019; 173: 478-85.
[http://dx.doi.org/10.1016/j.colsurfb.2018.10.020] [PMID: 30326364] 
[507] 
Zhang Y, Meng S, Ding J, Peng Q, Yu Y. Transition metal-coordinated graphitic carbon nitride dots as a sensitive and facile fluorescent probe for β-amyloid peptide detection. Analyst (Lond)  2019; 144(2): 504-11.
[http://dx.doi.org/10.1039/C8AN01620H] [PMID: 30474660] 
[508] 
Chen Y, Fan H, Xu C, Hu W, Yu B, Efficient Cholera Toxin B. Efficient Cholera Toxin B Subunit-Based Nanoparticles with MRI Capability for Drug Delivery to the Brain Following Intranasal Administration. Macromol Biosci  2019; 19(2): e1800340.
[http://dx.doi.org/10.1002/mabi.201800340] [PMID: 30536989] 
[509] 
Tabrizi MA, Ferré-Borrull J, Kapruwan P, Marsal LF. A photoelectrochemical sandwich immunoassay for protein S100β, a biomarker for Alzheimer’s disease, using an ITO electrode modified with a reduced graphene oxide-gold conjugate and CdS-labeled secondary antibody. Mikrochim Acta  2019; 186(2): 117.
[http://dx.doi.org/10.1007/s00604-018-3159-x] [PMID: 30649628] 
[510] 
Karthivashan G, Ganesan P, Park SY, Lee HW, Choi DK. Lipid-based nanodelivery approaches for dopamine-replacement therapies in Parkinson’s disease: From preclinical to translational studies. Biomaterials  2020; 232: 119704.
[http://dx.doi.org/10.1016/j.biomaterials.2019.119704] [PMID: 31901690] 
[511] 
Ling L, Jiang Y, Liu Y, et al. Role of gold nanoparticle from Cinnamomum verum against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced mice model. J Photochem Photobiol B  2019; 201: 111657.
[http://dx.doi.org/10.1016/j.jphotobiol.2019.111657] [PMID: 31706085] 
[512] 
Xue J, Liu T, Liu Y, et al. Neuroprotective effect of biosynthesised gold nanoparticles synthesised from root extract of Paeonia moutan against Parkinson disease - In vitro & in vivo model. J Photochem Photobiol B  2019; 200: 111635.
[http://dx.doi.org/10.1016/j.jphotobiol.2019.111635] [PMID: 31671372] 
[513] 
Pinto M, Fernandes C, Martins E, et al. Boosting Drug Discovery for Parkinson’s: Enhancement of the Delivery of a Monoamine Oxidase-B Inhibitor by Brain-Targeted PEGylated Polycaprolactone-Based Nanoparticles. Pharmaceutics  2019; 11(7): 11.
[http://dx.doi.org/10.3390/pharmaceutics11070331] [PMID: 31336891] 
[514] 
Gaba B, Khan T, Haider MF, et al. Vitamin E Loaded Naringenin Nanoemulsion via Intranasal Delivery for the Management of Oxidative Stress in a 6-OHDA Parkinson’s Disease Model. BioMed Res Int  2019; 2019: 2382563.
[http://dx.doi.org/10.1155/2019/2382563] [PMID: 31111044] 
[515] 
Li S, Liu J, Li G, et al. Near-infrared light-responsive, pramipexole-loaded biodegradable PLGA microspheres for therapeutic use in Parkinson’s disease. Eur J Pharm Biopharm  2019; 141: 1-11.
[http://dx.doi.org/10.1016/j.ejpb.2019.05.013] [PMID: 31100429] 
[516] 
Li X, Liu Q, Zhu D, Che Y, Feng X. Preparation of levodopa-loaded crystalsomes through thermally induced crystallization reverses functional deficits in Parkinsonian mice. Biomater Sci  2019; 7(4): 1623-31.
[http://dx.doi.org/10.1039/C8BM01098F] [PMID: 30702723] 
[517] 
Aly AE, Harmon BT, Padegimas L, Sesenoglu-Laird O, Cooper MJ, Waszczak BL. Intranasal Delivery of pGDNF DNA Nanoparticles Provides Neuroprotection in the Rat 6-Hydroxydopamine Model of Parkinson’s Disease. Mol Neurobiol  2019; 56(1): 688-701.
[http://dx.doi.org/10.1007/s12035-018-1109-6] [PMID: 29779176] 
[518] 
Rukmangathen R, Yallamalli I M, Yalavarthi P R. Biopharmaceutical Potential of Selegiline Loaded Chitosan Nanoparticles in the Management of Parkinson's Disease. Curr Drug Discov Technol  2019; 16: 417-25.
[519] 
Chen TW, Rajaji U, Chen SM, Li YL, Ramalingam RJ. Ultrasound-assisted synthesis of α-MnS (alabandite) nanoparticles decorated reduced graphene oxide hybrids: Enhanced electrocatalyst for electrochemical detection of Parkinson’s disease biomarker. Ultrason Sonochem  2019; 56: 378-85.
[http://dx.doi.org/10.1016/j.ultsonch.2019.04.010] [PMID: 31101276] 
[520] 
Shi Y, Liu Q, Yuan W, Xue M, Feng W, Li F. Dye-Assembled Upconversion Nanocomposite for Luminescence Ratiometric In Vivo Bioimaging of Copper Ions. ACS Appl Mater Interfaces  2019; 11(1): 430-6.
[http://dx.doi.org/10.1021/acsami.8b19961] [PMID: 30484307] 
[521] 
Sonuç Karaboğa MN, Sezgintürk MK. Cerebrospinal fluid levels of alpha-synuclein measured using a poly-glutamic acid-modified gold nanoparticle-doped disposable neuro-biosensor system. Analyst (Lond)  2019; 144(2): 611-21.
[http://dx.doi.org/10.1039/C8AN01279B] [PMID: 30457584] 
[522] 
Ji D, Xu N, Liu Z, et al. Smartphone-based differential pulse amperometry system for real-time monitoring of levodopa with carbon nanotubes and gold nanoparticles modified screen-printing electrodes. Biosens Bioelectron  2019; 129: 216-23.
[http://dx.doi.org/10.1016/j.bios.2018.09.082] [PMID: 30297172] 
[523] 
Love SA, Maurer-Jones MA, Thompson JW, Lin YS, Haynes CL. Assessing nanoparticle toxicity. Annu Rev Anal Chem (Palo Alto, Calif)  2012; 5: 181-205.
[http://dx.doi.org/10.1146/annurev-anchem-062011-143134] [PMID: 22524221] 
[524] 
Yildirimer L, Thanh NT, Loizidou M, Seifalian AM. Toxicology and clinical potential of nanoparticles. Nano Today  2011; 6(6): 585-607.
[http://dx.doi.org/10.1016/j.nantod.2011.10.001] [PMID: 23293661] 
[525] 
Kim Y, Park JH, Lee H, Nam JM. How Do the Size, Charge and Shape of Nanoparticles Affect Amyloid β Aggregation on Brain Lipid Bilayer? Sci Rep  2016; 6: 19548.
[http://dx.doi.org/10.1038/srep19548] [PMID: 26782664] 
[526] 
Batrakova EV, Li S, Alakhov VY, Miller DW, Kabanov AV. Optimal structure requirements for pluronic block copolymers in modifying P-glycoprotein drug efflux transporter activity in bovine brain microvessel endothelial cells. J Pharmacol Exp Ther  2003; 304(2): 845-54.
[http://dx.doi.org/10.1124/jpet.102.043307] [PMID: 12538842] 
[527] 
Ahmad J, Akhter S, Rizwanullah M, et al. Nanotechnology-based inhalation treatments for lung cancer: state of the art. Nanotechnol Sci Appl  2015; 8: 55-66.
[PMID: 26640374] 
[528] 
Kabanov AV, Batrakova EV, Alakhov VY. An essential relationship between ATP depletion and chemosensitizing activity of Pluronic block copolymers. J Control Release  2003; 91(1-2): 75-83.
[http://dx.doi.org/10.1016/S0168-3659(03)00211-6] [PMID: 12932639] 
[529] 
Bhabra G, Sood A, Fisher B, et al. Nanoparticles can cause DNA damage across a cellular barrier. Nat Nanotechnol  2009; 4(12): 876-83.
[http://dx.doi.org/10.1038/nnano.2009.313] [PMID: 19893513] 
[530] 
Moghimi SM, Andersen AJ, Hashemi SH, et al. Complement activation cascade triggered by PEG-PL engineered nanomedicines and carbon nanotubes: the challenges ahead. J Control Release  2010; 146(2): 175-81.
[http://dx.doi.org/10.1016/j.jconrel.2010.04.003] [PMID: 20388529] 
[531] 
Rozemuller JM, Bots GT, Roos RA, Eikelenboom P. Acute phase proteins but not activated microglial cells are present in parenchymal beta/A4 deposits in the brains of patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type. Neurosci Lett  1992; 140(2): 137-40.
[http://dx.doi.org/10.1016/0304-3940(92)90087-N] [PMID: 1380141] 
[532] 
McGeer PL, McGeer EG. The possible role of complement activation in Alzheimer disease. Trends Mol Med  2002; 8(11): 519-23.
[http://dx.doi.org/10.1016/S1471-4914(02)02422-X] [PMID: 12421685] 
[533] 
Giordano C, Albani D, Gloria A, et al. Nanocomposites for neurodegenerative diseases: hydrogel-nanoparticle combinations for a challenging drug delivery. Int J Artif Organs  2011; 34(12): 1115-27.
[http://dx.doi.org/10.5301/ijao.2011.8915] [PMID: 22198597] 
[534] 
Stern ST, Johnson DN. Role for nanomaterial-autophagy interaction in neurodegenerative disease. Autophagy  2008; 4(8): 1097-100.
[http://dx.doi.org/10.4161/auto.7142] [PMID: 18927490] 
[535] 
Hajipour MJ, Santoso MR, Rezaee F, Aghaverdi H, Mahmoudi M, Perry G. Advances in Alzheimer’s Diagnosis and Therapy: The Implications of Nanotechnology. Trends Biotechnol  2017; 35(10): 937-53.
[http://dx.doi.org/10.1016/j.tibtech.2017.06.002] [PMID: 28666544] 
[536] 
Yang FY, Lin YS, Kang KH, Chao TK. Reversible blood-brain barrier disruption by repeated transcranial focused ultrasound allows enhanced extravasation. J Control Release  2011; 150(1): 111-6.
[http://dx.doi.org/10.1016/j.jconrel.2010.10.038] [PMID: 21070825] 
[537] 
Choi JJ, Feshitan JA, Baseri B, et al. Microbubble-size dependence of focused ultrasound-induced blood-brain barrier opening in mice in vivo. IEEE Trans Biomed Eng  2010; 57(1): 145-54.
[http://dx.doi.org/10.1109/TBME.2009.2034533] [PMID: 19846365] 
[538] 
Bobo RH, Laske DW, Akbasak A, Morrison PF, Dedrick RL, Oldfield EH. Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci USA  1994; 91(6): 2076-80.
[http://dx.doi.org/10.1073/pnas.91.6.2076] [PMID: 8134351] 
[539] 
Eberling JL, Jagust WJ, Christine CW, et al. Results from a phase I safety trial of hAADC gene therapy for Parkinson disease. Neurology  2008; 70(21): 1980-3.
[http://dx.doi.org/10.1212/01.wnl.0000312381.29287.ff] [PMID: 18401019] 
[540] 
Boonruamkaew P, Chonpathompikunlert P, Vong LB, et al. Chronic treatment with a smart antioxidative nanoparticle for inhibition of amyloid plaque propagation in Tg2576 mouse model of Alzheimer’s disease. Sci Rep  2017; 7(1): 3785.
[http://dx.doi.org/10.1038/s41598-017-03411-7] [PMID: 28630497] 
[541] 
Boudreau RL, Rodríguez-Lebrón E, Davidson BL. RNAi medicine for the brain: progresses and challenges. Hum Mol Genet  2011; 20(R1): R21-7.
[http://dx.doi.org/10.1093/hmg/ddr137] [PMID: 21459775] 
[542] 
Santos T, Boto C, Saraiva CM, Bernardino L, Ferreira L. Nanomedicine Approaches to Modulate Neural Stem Cells in Brain Repair. Trends Biotechnol  2016; 34(6): 437-9.
[http://dx.doi.org/10.1016/j.tibtech.2016.02.003] [PMID: 26917252] 
[543] 
Hernando S, Gartziandia O, Herran E, Pedraz JL, Igartua M, Hernandez RM. Advances in nanomedicine for the treatment of Alzheimer’s and Parkinson’s diseases. Nanomedicine (Lond)  2016; 11(10): 1267-85.
[http://dx.doi.org/10.2217/nnm-2016-0019] [PMID: 27077453] 
[544] 
Kulkarni PV, Roney CA, Antich PP, Bonte FJ, Raghu AV, Aminabhavi TM. Quinoline-n-butylcyanoacrylate-based nanoparticles for brain targeting for the diagnosis of Alzheimer’s disease. Wiley Interdiscip Rev Nanomed Nanobiotechnol  2010; 2(1): 35-47.
[http://dx.doi.org/10.1002/wnan.59] [PMID: 20049829] 
[545] 
Roney CA, Arora V, Kulkarni PV, Antich PP, Bonte FJ. Nanoparticulate radiolabelled quinolines detect amyloid plaques in mouse models of Alzheimer’s disease. Int J Alzheimers Dis  2010; 2009: 2009.
[PMID: 20721294] 
[546] 
Härtig W, Kacza J, Paulke BR, et al. In vivo labelling of hippocampal beta-amyloid in triple-transgenic mice with a fluorescent acetylcholinesterase inhibitor released from nanoparticles. Eur J Neurosci  2010; 31(1): 99-109.
[http://dx.doi.org/10.1111/j.1460-9568.2009.07038.x] [PMID: 20092557] 
[547] 
Siegemund T, Paulke BR, Schmiedel H, et al. Thioflavins released from nanoparticles target fibrillar amyloid beta in the hippocampus of APP/PS1 transgenic mice. Int J Dev Neurosci  2006; 24(2-3): 195-201.
[http://dx.doi.org/10.1016/j.ijdevneu.2005.11.012] [PMID: 16386399] 
[548] 
Skaat H, Margel S. Synthesis of fluorescent-maghemite nanoparticles as multimodal imaging agents for amyloid-beta fibrils detection and removal by a magnetic field. Biochem Biophys Res Commun  2009; 386(4): 645-9.
[http://dx.doi.org/10.1016/j.bbrc.2009.06.110] [PMID: 19559008] 
[549] 
Fan S, Zheng Y, Liu X, et al. Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s disease. Drug Deliv  2018; 25(1): 1091-102.
[http://dx.doi.org/10.1080/10717544.2018.1461955] [PMID: 30107760] 
[550] 
Agyare EK, Jaruszewski KM, Curran GL, et al. Engineering theranostic nanovehicles capable of targeting cerebrovascular amyloid deposits. J Control Release  2014; 185: 121-9.
[http://dx.doi.org/10.1016/j.jconrel.2014.04.010] [PMID: 24735640] 
[551] 
Dehvari K, Lin KS. Synthesis, characterization and potential applications of multifunctional PEO-PPOPEO- magnetic drug delivery system. Curr Med Chem  2012; 19(30): 5199-204.
[http://dx.doi.org/10.2174/092986712803530584] [PMID: 23237189] 
[552] 
Skaat H, Corem-Slakmon E, Grinberg I, et al. Antibody-conjugated, dual-modal, near-infrared fluorescent iron oxide nanoparticles for antiamyloidgenic activity and specific detection of amyloid-β fibrils. Int J Nanomedicine  2013; 8: 4063-76.
[PMID: 24194640] 
[553] 
Zhang C, Wan X, Zheng X, et al. Dual-functional nanoparticles targeting amyloid plaques in the brains of Alzheimer’s disease mice. Biomaterials  2014; 35(1): 456-65.
[http://dx.doi.org/10.1016/j.biomaterials.2013.09.063] [PMID: 24099709] 
[554] 
Kumar J, Eraña H, López-Martínez E, et al. Detection of amyloid fibrils in Parkinson’s disease using plasmonic chirality. Proc Natl Acad Sci USA  2018; 115(13): 3225-30.
[http://dx.doi.org/10.1073/pnas.1721690115] [PMID: 29531058] 
[555] 
Herrmann Y, Bujnicki T, Zafiu C, et al. Nanoparticle standards for immuno-based quantitation of α-synuclein oligomers in diagnostics of Parkinson’s disease and other synucleinopathies. Clin Chim Acta  2017; 466: 152-9.
[http://dx.doi.org/10.1016/j.cca.2017.01.010] [PMID: 28088342] 
Cite As
Current Pharmaceutical Design

Nanomedicine against Alzheimer’s and Parkinson’s Disease

Abstract
