Generic placeholder image

Current Neuropharmacology

Author(s): Stéphanie Pain, Sébastien Brot and Afsaneh Gaillard*

DOI: 10.2174/1570159X19666210906120302

DownloadDownload PDF Flyer Cite As
Neuroprotective Effects of Neuropeptide Y against Neurodegenerative Disease

Page: [1717 - 1725] Pages: 9

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Neuropeptide Y (NPY), a 36 amino acid peptide, is widely expressed in the mammalian brain. Changes in NPY levels in different brain regions and plasma have been described in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, and Machado-Joseph disease. The changes in NPY levels may reflect the attempt to set up an endogenous neuroprotective mechanism to counteract the degenerative process. Accumulating evidence indicates that NPY can function as an anti-apoptotic, anti-inflammatory, and pro-phagocytic agent, which may be used effectively to halt or to slow down the progression of the disease. In this review, we will focus on the neuroprotective roles of NPY in several neuropathological conditions, with a particular focus on the anti-inflammatory properties of NPY.

Keywords: Neuropeptide Y, neurodegenerative disease, neuroprotection, neuroinflammation, apoptosis, autophagy.

Graphical Abstract

[1]
Adrian, T.E.; Allen, J.M.; Bloom, S.R.; Ghatei, M.A.; Rossor, M.N.; Roberts, G.W.; Crow, T.J.; Tatemoto, K.; Polak, J.M. Neuropeptide Y distribution in human brain. Nature, 1983, 306(5943), 584-586.
[http://dx.doi.org/10.1038/306584a0] [PMID: 6358901]
[2]
Wettstein, J.G.; Earley, B.; Junien, J.L. Central nervous system pharmacology of neuropeptide Y. Pharmacol. Ther., 1995, 65(3), 397-414.
[http://dx.doi.org/10.1016/0163-7258(95)98598-K] [PMID: 7644568]
[3]
Silva, A.P.; Cavadas, C.; Grouzmann, E. Neuropeptide Y and its receptors as potential therapeutic drug targets. Clin. Chim. Acta, 2002, 326(1-2), 3-25.
[http://dx.doi.org/10.1016/S0009-8981(02)00301-7] [PMID: 12417094]
[4]
Duarte-Neves, J.; Pereira de Almeida, L.; Cavadas, C.; Neuropeptide, Y.; Neuropeptide, Y. NPY) as a therapeutic target for neurodegenerative diseases. Neurobiol. Dis., 2016, 95, 210-224.
[http://dx.doi.org/10.1016/j.nbd.2016.07.022] [PMID: 27461050]
[5]
Silva, A.P.; Pinheiro, P.S.; Carvalho, A.P.; Carvalho, C.M.; Jakobsen, B.; Zimmer, J.; Malva, J.O. Activation of neuropeptide Y receptors is neuroprotective against excitotoxicity in organotypic hippocampal slice cultures. FASEB J., 2003, 17(9), 1118-1120.
[http://dx.doi.org/10.1096/fj.02-0885fje] [PMID: 12692082]
[6]
Alvaro, A.R.; Martins, J.; Costa, A.C.; Fernandes, E.; Carvalho, F.; Ambrósio, A.F.; Cavadas, C. Neuropeptide Y protects retinal neural cells against cell death induced by ecstasy. Neuroscience, 2008, 152(1), 97-105.
[http://dx.doi.org/10.1016/j.neuroscience.2007.12.027] [PMID: 18249070]
[7]
Rose, J.B.; Crews, L.; Rockenstein, E.; Adame, A.; Mante, M.; Hersh, L.B.; Gage, F.H.; Spencer, B.; Potkar, R.; Marr, R.A.; Masliah, E. Neuropeptide Y fragments derived from neprilysin processing are neuroprotective in a transgenic model of Alzheimer’s disease. J. Neurosci., 2009, 29(4), 1115-1125.
[http://dx.doi.org/10.1523/JNEUROSCI.4220-08.2009] [PMID: 19176820]
[8]
Thiriet, N.; Deng, X.; Solinas, M.; Ladenheim, B.; Curtis, W.; Goldberg, S.R.; Palmiter, R.D.; Cadet, J.L. Neuropeptide Y protects against methamphetamine-induced neuronal apoptosis in the mouse striatum. J. Neurosci., 2005, 25(22), 5273-5279.
[http://dx.doi.org/10.1523/JNEUROSCI.4893-04.2005] [PMID: 15930374]
[9]
Pringsheim, T.; Jette, N.; Frolkis, A.; Steeves, T.D.L. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov. Disord., 2014, 29(13), 1583-1590.
[http://dx.doi.org/10.1002/mds.25945] [PMID: 24976103]
[10]
Fahn, S. Description of Parkinson’s disease as a clinical syndrome. Ann. N. Y. Acad. Sci., 2003, 991, 1-14.
[http://dx.doi.org/10.1111/j.1749-6632.2003.tb07458.x] [PMID: 12846969]
[11]
Jankovic, J. Parkinson’s disease: clinical features and diagnosis. J. Neurol. Neurosurg. Psychiatry, 2008, 79(4), 368-376.
[http://dx.doi.org/10.1136/jnnp.2007.131045] [PMID: 18344392]
[12]
Spillantini, M.G.; Schmidt, M.L.; Lee, V.M.; Trojanowski, J.Q.; Jakes, R.; Goedert, M. Alpha-synuclein in Lewy bodies. Nature, 1997, 388(6645), 839-840.
[http://dx.doi.org/10.1038/42166] [PMID: 9278044]
[13]
Poewe, W.; Seppi, K.; Tanner, C.M.; Halliday, G.M.; Brundin, P.; Volkmann, J.; Schrag, A-E.; Lang, A.E. Parkinson disease. Nat. Rev. Dis. Primers, 2017, 3, 17013.
[http://dx.doi.org/10.1038/nrdp.2017.13] [PMID: 28332488]
[14]
Marsden, C.D. Parkinson’s disease. Lancet, 1990, 335(8695), 948-952.
[http://dx.doi.org/10.1016/0140-6736(90)91006-V] [PMID: 1691427]
[15]
Ross, G.W.; Petrovitch, H.; Abbott, R.D.; Nelson, J.; Markesbery, W.; Davis, D.; Hardman, J.; Launer, L.; Masaki, K.; Tanner, C.M.; White, L.R. Parkinsonian signs and substantia nigra neuron density in decendents elders without PD. Ann. Neurol., 2004, 56(4), 532-539.
[http://dx.doi.org/10.1002/ana.20226] [PMID: 15389895]
[16]
Lang, A.E.; Lozano, A.M. Parkinson’s disease. First of two parts. N. Engl. J. Med., 1998, 339(15), 1044-1053.
[http://dx.doi.org/10.1056/NEJM199810083391506] [PMID: 9761807]
[17]
Dauer, W.; Przedborski, S. Parkinson’s disease: mechanisms and models. Neuron, 2003, 39(6), 889-909.
[http://dx.doi.org/10.1016/S0896-6273(03)00568-3] [PMID: 12971891]
[18]
Bergman, H.; Wichmann, T.; DeLong, M.R. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science, 1990, 249(4975), 1436-1438.
[http://dx.doi.org/10.1126/science.2402638] [PMID: 2402638]
[19]
Gaillard, A.; Decressac, M.; Frappé, I.; Fernagut, P.O.; Prestoz, L.; Besnard, S.; Jaber, M. Anatomical and functional reconstruction of the nigrostriatal pathway by intranigral transplants. Neurobiol. Dis., 2009, 35(3), 477-488.
[http://dx.doi.org/10.1016/j.nbd.2009.07.003] [PMID: 19616502]
[20]
Gaillard, A.; Jaber, M. Rewiring the brain with cell transplantation in Parkinson’s disease. Trends Neurosci., 2011, 34(3), 124-133.
[http://dx.doi.org/10.1016/j.tins.2011.01.003] [PMID: 21316770]
[21]
Ma, Y.; Zhan, M.; OuYang, L.; Li, Y.; Chen, S.; Wu, J.; Chen, J.; Luo, C.; Lei, W. The effects of unilateral 6-OHDA lesion in medial forebrain bundle on the motor, cognitive dysfunctions and vulnerability of different striatal interneuron types in rats. Behav. Brain Res., 2014, 266, 37-45.
[http://dx.doi.org/10.1016/j.bbr.2014.02.039] [PMID: 24613235]
[22]
Cannizzaro, C.; Tel, B.C.; Rose, S.; Zeng, B-Y.; Jenner, P. Increased neuropeptide Y mRNA expression in striatum in Parkinson’s disease. Brain Res. Mol. Brain Res., 2003, 110(2), 169-176.
[http://dx.doi.org/10.1016/S0169-328X(02)00555-7] [PMID: 12591154]
[23]
Decressac, M.; Pain, S.; Chabeauti, P-Y.; Frangeul, L.; Thiriet, N.; Herzog, H.; Vergote, J.; Chalon, S.; Jaber, M.; Gaillard, A. Neuroprotection by neuropeptide Y in cell and animal models of Parkinson’s disease. Neurobiol. Aging, 2012, 33(9), 2125-2137.
[http://dx.doi.org/10.1016/j.neurobiolaging.2011.06.018] [PMID: 21816512]
[24]
Pain, S.; Vergote, J.; Gulhan, Z.; Bodard, S.; Chalon, S.; Gaillard, A. Inflammatory process in Parkinson disease: neuroprotection by neuropeptide Y. Fundam. Clin. Pharmacol., 2019, 33(5), 544-548.
[http://dx.doi.org/10.1111/fcp.12464] [PMID: 30866091]
[25]
Burns, A.; Iliffe, S. Alzheimer’s disease. BMJ, 2009, 338, b158.
[http://dx.doi.org/10.1136/bmj.b158] [PMID: 19196745]
[26]
Tiraboschi, P.; Hansen, L.A.; Thal, L.J.; Corey-Bloom, J. The importance of neuritic plaques and tangles to the development and evolution of AD. Neurology, 2004, 62(11), 1984-1989.
[http://dx.doi.org/10.1212/01.WNL.0000129697.01779.0A] [PMID: 15184601]
[27]
Mahar, I.; Albuquerque, M.S.; Mondragon-Rodriguez, S.; Cavanagh, C.; Davoli, M.A.; Chabot, J-G.; Williams, S.; Mechawar, N.; Quirion, R.; Krantic, S. Phenotypic alterations in hippocampal NPY- and PV-expressing interneurons in a presymptomatic transgenic mouse model of Alzheimer’s disease. Front. Aging Neurosci., 2017, 8, 327.
[http://dx.doi.org/10.3389/fnagi.2016.00327] [PMID: 28154533]
[28]
Ramos, B.; Baglietto-Vargas, D.; del Rio, J.C.; Moreno-Gonzalez, I.; Santa-Maria, C.; Jimenez, S.; Caballero, C.; Lopez-Tellez, J.F.; Khan, Z.U.; Ruano, D.; Gutierrez, A.; Vitorica, J. Early neuropathology of somatostatin/NPY GABAergic cells in the hippocampus of a PS1xAPP transgenic model of Alzheimer’s disease. Neurobiol. Aging, 2006, 27(11), 1658-1672.
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.09.022] [PMID: 16271420]
[29]
Kowall, N.W.; Beal, M.F. Cortical somatostatin, neuropeptide Y, and NADPH diaphorase neurons: normal anatomy and alterations in Alzheimer’s disease. Ann. Neurol., 1988, 23(2), 105-114.
[http://dx.doi.org/10.1002/ana.410230202] [PMID: 2897822]
[30]
Martel, J.C.; Alagar, R.; Robitaille, Y.; Quirion, R. Neuropeptide Y receptor binding sites in human brain. Possible alteration in Alzheimer’s disease. Brain Res., 1990, 519(1-2), 228-235.
[http://dx.doi.org/10.1016/0006-8993(90)90082-M] [PMID: 2168782]
[31]
Alom, J.; Galard, R.; Catalan, R.; Castellanos, J.M.; Schwartz, S.; Tolosa, E. Cerebrospinal fluid neuropeptide Y in Alzheimer’s disease. Eur. Neurol., 1990, 30(4), 207-210.
[http://dx.doi.org/10.1159/000117347] [PMID: 2209674]
[32]
Koide, S.; Onishi, H.; Hashimoto, H.; Kai, T.; Yamagami, S. Plasma neuropeptide Y is reduced in patients with Alzheimer’s disease. Neurosci. Lett., 1995, 198(2), 149-151.
[http://dx.doi.org/10.1016/0304-3940(95)11973-Z] [PMID: 8592643]
[33]
dos Santos, V.V.; Santos, D.B.; Lach, G.; Rodrigues, A.L.S.; Farina, M.; De Lima, T.C.M.; Prediger, R.D.; Neuropeptide, Y.; Neuropeptide, Y. NPY) prevents depressive-like behavior, spatial memory deficits and oxidative stress following amyloid-β (Aβ(1-40)) administration in mice. Behav. Brain Res., 2013, 244, 107-115.
[http://dx.doi.org/10.1016/j.bbr.2013.01.039] [PMID: 23396168]
[34]
Dawbarn, D.; De Quidt, M.E.; Emson, P.C. Survival of basal ganglia neuropeptide Y-somatostatin neurones in Huntington’s disease. Brain Res., 1985, 340(2), 251-260.
[http://dx.doi.org/10.1016/0006-8993(85)90921-7] [PMID: 2862959]
[35]
Decressac, M.; Wright, B.; Tyers, P.; Gaillard, A.; Barker, R.A. Neuropeptide Y modifies the disease course in the R6/2 transgenic model of Huntington’s disease. Exp. Neurol., 2010, 226(1), 24-32.
[http://dx.doi.org/10.1016/j.expneurol.2010.07.022] [PMID: 20673761]
[36]
Fatoba, O.; Kloster, E.; Reick, C.; Saft, C.; Gold, R.; Epplen, J.T.; Arning, L.; Ellrichmann, G. Activation of NPY-Y2 receptors ameliorates disease pathology in the R6/2 mouse and PC12 cell models of Huntington’s disease. Exp. Neurol., 2018, 302, 112-128.
[http://dx.doi.org/10.1016/j.expneurol.2018.01.001] [PMID: 29309751]
[37]
Chiò, A.; Logroscino, G.; Traynor, B.J.; Collins, J.; Simeone, J.C.; Goldstein, L.A.; White, L.A. Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology, 2013, 41(2), 118-130.
[http://dx.doi.org/10.1159/000351153] [PMID: 23860588]
[38]
Taylor, J.P.; Brown, R.H., Jr; Cleveland, D.W. Decoding ALS: from genes to mechanism. Nature, 2016, 539(7628), 197-206.
[http://dx.doi.org/10.1038/nature20413] [PMID: 27830784]
[39]
Clark, R.M.; Blizzard, C.A.; Young, K.M.; King, A.E.; Dickson, T.C. Calretinin and Neuropeptide Y interneurons are differentially altered in the motor cortex of the SOD1G93A mouse model of ALS. Sci. Rep., 2017, 7, 44461.
[http://dx.doi.org/10.1038/srep44461] [PMID: 28294153]
[40]
Ahmed, R.M.; Phan, K.; Highton-Williamson, E.; Strikwerda-Brown, C.; Caga, J.; Ramsey, E.; Zoing, M.; Devenney, E.; Kim, W.S.; Hodges, J.R.; Piguet, O.; Halliday, G.M.; Kiernan, M.C. Eating peptides: biomarkers of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia. Ann. Clin. Transl. Neurol., 2019, 6(3), 486-495.
[http://dx.doi.org/10.1002/acn3.721] [PMID: 30911572]
[41]
Clark, C.M.; Clark, R.M.; Hoyle, J.A.; Dickson, T.C. Pathogenic or protective? Neuropeptide Y in amyotrophic lateral sclerosis. J. Neurochem., 2021, 156(3), 273-289.
[http://dx.doi.org/10.1111/jnc.15125] [PMID: 32654149]
[42]
Paulson, H.L. Dominantly inherited ataxias: lessons learned from Machado-Joseph disease/spinocerebellar ataxia type 3. Semin. Neurol., 2007, 27(2), 133-142.
[http://dx.doi.org/10.1055/s-2007-971172] [PMID: 17390258]
[43]
Kawaguchi, Y.; Okamoto, T.; Taniwaki, M.; Aizawa, M.; Inoue, M.; Katayama, S.; Kawakami, H.; Nakamura, S.; Nishimura, M.; Akiguchi, I. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat. Genet., 1994, 8(3), 221-228.
[http://dx.doi.org/10.1038/ng1194-221] [PMID: 7874163]
[44]
Duarte-Neves, J.; Gonçalves, N.; Cunha-Santos, J.; Simões, A.T.; den Dunnen, W.F.A.; Hirai, H.; Kügler, S.; Cavadas, C.; Pereira de Almeida, L. Neuropeptide Y mitigates neuropathology and motor deficits in mouse models of Machado-Joseph disease. Hum. Mol. Genet., 2015, 24(19), 5451-5463.
[http://dx.doi.org/10.1093/hmg/ddv271] [PMID: 26220979]
[45]
Duarte-Neves, J.; Cavadas, C.; Pereira de Almeida, L.; Neuropeptide, Y.; Neuropeptide, Y. NPY) intranasal delivery alleviates Machado-Joseph disease. Sci. Rep., 2021, 11(1), 3345.
[http://dx.doi.org/10.1038/s41598-021-82339-5] [PMID: 33558582]
[46]
Silva, A.P.; Xapelli, S.; Grouzmann, E.; Cavadas, C. The putative neuroprotective role of neuropeptide Y in the central nervous system. Curr. Drug Targets CNS Neurol. Disord., 2005, 4(4), 331-347.
[http://dx.doi.org/10.2174/1568007054546153] [PMID: 16101553]
[47]
Smiałowska, M.; Domin, H.; Zieba, B.; Koźniewska, E.; Michalik, R.; Piotrowski, P.; Kajta, M. Neuroprotective effects of neuropeptide Y-Y2 and Y5 receptor agonists in vitro and in vivo. Neuropeptides, 2009, 43(3), 235-249.
[http://dx.doi.org/10.1016/j.npep.2009.02.002] [PMID: 19318226]
[48]
Xapelli, S.; Silva, A.P.; Ferreira, R.; Malva, J.O. Neuropeptide Y can rescue neurons from cell death following the application of an excitotoxic insult with kainate in rat organotypic hippocampal slice cultures. Peptides, 2007, 28(2), 288-294.
[http://dx.doi.org/10.1016/j.peptides.2006.09.031] [PMID: 17212973]
[49]
Santos-Carvalho, A.; Elvas, F.; Alvaro, A.R.; Ambrósio, A.F.; Cavadas, C. Neuropeptide Y receptors activation protects rat retinal neural cells against necrotic and apoptotic cell death induced by glutamate. Cell Death Dis., 2013, 4, e636.
[http://dx.doi.org/10.1038/cddis.2013.160] [PMID: 23681231]
[50]
Rothstein, J.D.; Tsai, G.; Kuncl, R.W.; Clawson, L.; Cornblath, D.R.; Drachman, D.B.; Pestronk, A.; Stauch, B.L.; Coyle, J.T. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann. Neurol., 1990, 28(1), 18-25.
[http://dx.doi.org/10.1002/ana.410280106] [PMID: 2375630]
[51]
Shaw, P.J.; Forrest, V.; Ince, P.G.; Richardson, J.P.; Wastell, H.J. CSF and plasma amino acid levels in motor neuron disease: elevation of CSF glutamate in a subset of patients. Neurodegeneration, 1995, 4(2), 209-216.
[http://dx.doi.org/10.1006/neur.1995.0026] [PMID: 7583686]
[52]
Hirsch, E.C.; Hunot, S. Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol., 2009, 8(4), 382-397.
[http://dx.doi.org/10.1016/S1474-4422(09)70062-6] [PMID: 19296921]
[53]
Amor, S.; Puentes, F.; Baker, D.; van der Valk, P. Inflammation in neurodegenerative diseases. Immunology, 2010, 129(2), 154-169.
[http://dx.doi.org/10.1111/j.1365-2567.2009.03225.x] [PMID: 20561356]
[54]
Bartels, A.L.; Leenders, K.L. Cyclooxygenase and neuroinflammation in Parkinson’s disease neurodegeneration. Curr. Neuropharmacol., 2010, 8(1), 62-68.
[http://dx.doi.org/10.2174/157015910790909485] [PMID: 20808546]
[55]
Bovolenta, R.; Zucchini, S.; Paradiso, B.; Rodi, D.; Merigo, F.; Navarro Mora, G.; Osculati, F.; Berto, E.; Marconi, P.; Marzola, A.; Fabene, P.F.; Simonato, M. Hippocampal FGF-2 and BDNF overexpression attenuates epileptogenesis-associated neuroinflammation and reduces spontaneous recurrent seizures. J. Neuroinflammation, 2010, 7, 81.
[http://dx.doi.org/10.1186/1742-2094-7-81] [PMID: 21087489]
[56]
Wu, S-Y.; Wang, T-F.; Yu, L.; Jen, C.J.; Chuang, J-I.; Wu, F-S.; Wu, C-W.; Kuo, Y-M. Running exercise protects the substantia nigra dopaminergic neurons against inflammation-induced degeneration via the activation of BDNF signaling pathway. Brain Behav. Immun., 2011, 25(1), 135-146.
[http://dx.doi.org/10.1016/j.bbi.2010.09.006] [PMID: 20851176]
[57]
Xapelli, S.; Bernardino, L.; Ferreira, R.; Grade, S.; Silva, A.P.; Salgado, J.R.; Cavadas, C.; Grouzmann, E.; Poulsen, F.R.; Jakobsen, B.; Oliveira, C.R.; Zimmer, J.; Malva, J.O. Interaction between neuropeptide Y (NPY) and brain-derived neurotrophic factor in NPY-mediated neuroprotection against excitotoxicity: a role for microglia. Eur. J. Neurosci., 2008, 27(8), 2089-2102.
[http://dx.doi.org/10.1111/j.1460-9568.2008.06172.x] [PMID: 18412629]
[58]
Maeda, K.; Yasuda, M.; Kaneda, H.; Maeda, S.; Yamadori, A. Cerebrospinal fluid (CSF) neuropeptide Y- and somatostatin-like immunoreactivities in man. Neuropeptides, 1994, 27(6), 323-332.
[http://dx.doi.org/10.1016/0143-4179(94)90058-2] [PMID: 7898640]
[59]
Bedoui, S.; Miyake, S.; Lin, Y.; Miyamoto, K.; Oki, S.; Kawamura, N.; Beck-Sickinger, A.; von Hörsten, S.; Yamamura, T.; Neuropeptide, Y.; Neuropeptide, Y. NPY) suppresses experimental autoimmune encephalomyelitis: NPY1 receptor-specific inhibition of autoreactive Th1 responses in vivo. J. Immunol., 2003, 171(7), 3451-3458.
[http://dx.doi.org/10.4049/jimmunol.171.7.3451] [PMID: 14500640]
[60]
Kowiański, P.; Lietzau, G.; Czuba, E.; Waśkow, M.; Steliga, A.; Moryś, J. BDNF: A key factor with multipotent impact on brain signaling and synaptic plasticity. Cell. Mol. Neurobiol., 2018, 38(3), 579-593.
[http://dx.doi.org/10.1007/s10571-017-0510-4] [PMID: 28623429]
[61]
Eyileten, C.; Sharif, L.; Wicik, Z.; Jakubik, D.; Jarosz-Popek, J.; Soplinska, A.; Postula, M.; Czlonkowska, A.; Kaplon-Cieslicka, A.; Mirowska-Guzel, D. The relation of the brain-derived neurotrophic factor with microRNAs in neurodegenerative diseases and ischemic stroke. Mol. Neurobiol., 2021, 58(1), 329-347.
[http://dx.doi.org/10.1007/s12035-020-02101-2] [PMID: 32944919]
[62]
Reibel, S.; Larmet, Y.; Lê, B.T.; Carnahan, J.; Marescaux, C.; Depaulis, A. Brain-derived neurotrophic factor delays hippocampal kindling in the rat. Neuroscience, 2000, 100(4), 777-788.
[http://dx.doi.org/10.1016/S0306-4522(00)00351-1] [PMID: 11036211]
[63]
Koyama, R.; Ikegaya, Y. To BDNF or not to BDNF: that is the epileptic hippocampus. Neuroscientist, 2005, 11(4), 282-287.
[http://dx.doi.org/10.1177/1073858405278266] [PMID: 16061515]
[64]
Takahashi, M.; Hayashi, S.; Kakita, A.; Wakabayashi, K.; Fukuda, M.; Kameyama, S.; Tanaka, R.; Takahashi, H.; Nawa, H. Patients with temporal lobe epilepsy show an increase in brain-derived neurotrophic factor protein and its correlation with neuropeptide Y. Brain Res., 1999, 818(2), 579-582.
[http://dx.doi.org/10.1016/S0006-8993(98)01355-9] [PMID: 10082852]
[65]
Croce, N.; Gelfo, F.; Ciotti, M.T.; Federici, G.; Caltagirone, C.; Bernardini, S.; Angelucci, F. NPY modulates miR-30a-5p and BDNF in opposite direction in an in vitro model of Alzheimer disease: a possible role in neuroprotection? Mol. Cell. Biochem., 2013, 376(1-2), 189-195.
[http://dx.doi.org/10.1007/s11010-013-1567-0] [PMID: 23358924]
[66]
McKhann, G.; Drachman, D.; Folstein, M.; Katzman, R.; Price, D.; Stadlan, E.M. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology, 1984, 34(7), 939-944.
[http://dx.doi.org/10.1212/WNL.34.7.939] [PMID: 6610841]
[67]
Jellinger, K.A. Pathology of Parkinson’s disease. Changes other than the nigrostriatal pathway. Mol. Chem. Neuropathol., 1991, 14(3), 153-197.
[http://dx.doi.org/10.1007/BF03159935] [PMID: 1958262]
[68]
DiFiglia, M.; Sapp, E.; Chase, K.O.; Davies, S.W.; Bates, G.P.; Vonsattel, J.P.; Aronin, N. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science, 1997, 277(5334), 1990-1993.
[http://dx.doi.org/10.1126/science.277.5334.1990] [PMID: 9302293]
[69]
Paulson, H.L.; Perez, M.K.; Trottier, Y.; Trojanowski, J.Q.; Subramony, S.H.; Das, S.S.; Vig, P.; Mandel, J.L.; Fischbeck, K.H.; Pittman, R.N. Intranuclear inclusions of expanded polyglutamine protein in spinocerebellar ataxia type 3. Neuron, 1997, 19(2), 333-344.
[http://dx.doi.org/10.1016/S0896-6273(00)80943-5] [PMID: 9292723]
[70]
Schmidt, T.; Landwehrmeyer, G.B.; Schmitt, I.; Trottier, Y.; Auburger, G.; Laccone, F.; Klockgether, T.; Völpel, M.; Epplen, J.T.; Schöls, L.; Riess, O. An isoform of ataxin-3 accumulates in the nucleus of neuronal cells in affected brain regions of SCA3 patients. Brain Pathol., 1998, 8(4), 669-679.
[http://dx.doi.org/10.1111/j.1750-3639.1998.tb00193.x] [PMID: 9804376]
[71]
Nixon, R.A. The role of autophagy in neurodegenerative disease. Nat. Med., 2013, 19(8), 983-997.
[http://dx.doi.org/10.1038/nm.3232] [PMID: 23921753]
[72]
Aveleira, C.A.; Botelho, M.; Cavadas, C. NPY/neuropeptide Y enhances autophagy in the hypothalamus: a mechanism to delay aging? Autophagy, 2015, 11(8), 1431-1433.
[http://dx.doi.org/10.1080/15548627.2015.1062202] [PMID: 26086271]
[73]
Aveleira, C.A.; Botelho, M.; Carmo-Silva, S.; Pascoal, J.F.; Ferreira-Marques, M.; Nóbrega, C.; Cortes, L.; Valero, J.; Sousa-Ferreira, L.; Álvaro, A.R.; Santana, M.; Kügler, S.; Pereira de Almeida, L.; Cavadas, C. Neuropeptide Y stimulates autophagy in hypothalamic neurons. Proc. Natl. Acad. Sci. USA, 2015, 112(13), E1642-E1651.
[http://dx.doi.org/10.1073/pnas.1416609112] [PMID: 25775546]
[74]
Mattson, M.P. Apoptosis in neurodegenerative disorders. Nat. Rev. Mol. Cell Biol., 2000, 1(2), 120-129.
[http://dx.doi.org/10.1038/35040009] [PMID: 11253364]
[75]
Lee, D.Y.; Hong, S.H.; Kim, B.; Lee, D-S.; Yu, K.; Lee, K-S. Neuropeptide Y mitigates ER stress-induced neuronal cell death by activating the PI3K-XBP1 pathway. Eur. J. Cell Biol., 2018, 97(5), 339-348.
[http://dx.doi.org/10.1016/j.ejcb.2018.04.003] [PMID: 29650257]
[76]
Yarosh, H.L.; Angulo, J.A. Modulation of methamphetamine-induced nitric oxide production by neuropeptide Y in the murine striatum. Brain Res., 2012, 1483, 31-38.
[http://dx.doi.org/10.1016/j.brainres.2012.09.013] [PMID: 22982589]
[77]
Kir, H.M.; Sahin, D.; Oztaş, B.; Musul, M.; Kuskay, S. Effects of single-dose neuropeptide Y on levels of hippocampal BDNF, MDA, GSH, and NO in a rat model of pentylenetetrazole-induced epileptic seizure. Bosn. J. Basic Med. Sci., 2013, 13(4), 242-247.
[http://dx.doi.org/10.17305/bjbms.2013.2332] [PMID: 24289760]
[78]
Drechsel, D.A.; Estévez, A.G.; Barbeito, L.; Beckman, J.S. Nitric oxide-mediated oxidative damage and the progressive demise of motor neurons in ALS. Neurotox. Res., 2012, 22(4), 251-264.
[http://dx.doi.org/10.1007/s12640-012-9322-y] [PMID: 22488161]
[79]
Calabrese, E.J.; Baldwin, L.A. Defining hormesis. Hum. Exp. Toxicol., 2002, 21(2), 91-97.
[http://dx.doi.org/10.1191/0960327102ht217oa] [PMID: 12102503]
[80]
Calabrese, E.J.; Bachmann, K.A.; Bailer, A.J.; Bolger, P.M.; Borak, J.; Cai, L.; Cedergreen, N.; Cherian, M.G.; Chiueh, C.C.; Clarkson, T.W.; Cook, R.R.; Diamond, D.M.; Doolittle, D.J.; Dorato, M.A.; Duke, S.O.; Feinendegen, L.; Gardner, D.E.; Hart, R.W.; Hastings, K.L.; Hayes, A.W.; Hoffmann, G.R.; Ives, J.A.; Jaworowski, Z.; Johnson, T.E.; Jonas, W.B.; Kaminski, N.E.; Keller, J.G.; Klaunig, J.E.; Knudsen, T.B.; Kozumbo, W.J.; Lettieri, T.; Liu, S.Z.; Maisseu, A.; Maynard, K.I.; Masoro, E.J.; McClellan, R.O.; Mehendale, H.M.; Mothersill, C.; Newlin, D.B.; Nigg, H.N.; Oehme, F.W.; Phalen, R.F.; Philbert, M.A.; Rattan, S.I.; Riviere, J.E.; Rodricks, J.; Sapolsky, R.M.; Scott, B.R.; Seymour, C.; Sinclair, D.A.; Smith-Sonneborn, J.; Snow, E.T.; Spear, L.; Stevenson, D.E.; Thomas, Y.; Tubiana, M.; Williams, G.M.; Mattson, M.P. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. Toxicol. Appl. Pharmacol., 2007, 222(1), 122-128.
[http://dx.doi.org/10.1016/j.taap.2007.02.015] [PMID: 17459441]
[81]
Calabrese, V.; Cornelius, C.; Dinkova-Kostova, A.T.; Calabrese, E.J.; Mattson, M.P. Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid. Redox Signal., 2010, 13(11), 1763-1811.
[http://dx.doi.org/10.1089/ars.2009.3074] [PMID: 20446769]
[82]
Govindan, S.; Amirthalingam, M.; Duraisamy, K.; Govindhan, T.; Sundararaj, N.; Palanisamy, S. Phytochemicals-induced hormesis protects Caenorhabditis elegans against α-synuclein protein aggregation and stress through modulating HSF-1 and SKN-1/Nrf2 signaling pathways. Biomed. Pharmacother., 2018, 102, 812-822.
[http://dx.doi.org/10.1016/j.biopha.2018.03.128] [PMID: 29605769]
[83]
Brunetti, G.; Di Rosa, G.; Scuto, M.; Leri, M.; Stefani, M.; Schmitz-Linneweber, C.; Calabrese, V.; Saul, N. Healthspan maintenance and prevention of Parkinson’s-like phenotypes with hydroxytyrosol and oleuropein aglycone in C. elegans. Int. J. Mol. Sci., 2020, 21(7), E2588.
[http://dx.doi.org/10.3390/ijms21072588] [PMID: 32276415]
[84]
Siracusa, R.; Scuto, M.; Fusco, R.; Trovato, A.; Ontario, M.L.; Crea, R.; Di Paola, R.; Cuzzocrea, S.; Calabrese, V. Anti-inflammatory and anti-oxidant activity of hidrox® in rotenone-induced Parkinson’s disease in Mice. Antioxidants, 2020, 9(9), E824.
[http://dx.doi.org/10.3390/antiox9090824] [PMID: 32899274]
[85]
Marini, A.M.; Jiang, H.; Pan, H.; Wu, X.; Lipsky, R.H. Hormesis: a promising strategy to sustain endogenous neuronal survival pathways against neurodegenerative disorders. Ageing Res. Rev., 2008, 7(1), 21-33.
[http://dx.doi.org/10.1016/j.arr.2007.07.003] [PMID: 17889623]
[86]
Yulyaningsih, E.; Zhang, L.; Herzog, H.; Sainsbury, A. NPY receptors as potential targets for anti-obesity drug development. Br. J. Pharmacol., 2011, 163(6), 1170-1202.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01363.x] [PMID: 21545413]
[87]
Lochhead, J.J.; Thorne, R.G. Intranasal delivery of biologics to the central nervous system. Adv. Drug Deliv. Rev., 2012, 64(7), 614-628.
[http://dx.doi.org/10.1016/j.addr.2011.11.002] [PMID: 22119441]