The Effects of Curcumin on Astrocytes in Common Neurodegenerative
Conditions

Ameer   A.   Alameri; Muhammad   Usman   Ghanni; Arsalan      Ali; Mandeep      Singh; Moaed   E.   Al-Gazally; Abbas   F.   Almulla; Andrés      Alexis Ramírez-Coronel; Yasser   Fakri   Mustafa; Reena      Gupta; Rasha   Fadhel   Obaid; Gamal   A.   Gabr; Bagher      Farhood
Abstract

Neurodegenerative diseases are age-related, multifactorial, and complicated conditions that affect the nervous system. In most cases, these diseases may begin with an accumulation of misfolded proteins rather than decay before they develop clinical symptoms. The progression of these diseases can be influenced by a number of internal and external factors, including oxidative damage, neuro-inflammation, and the accumulation of misfolded amyloid proteins. Astrocytes, with the highest abundance among the cells of the mammalian central nervous system, perform several important activities, such as maintaining brain homeostasis and playing a role in the neurodegenerative condition onset and progress. Therefore, these cells have been considered to be potential targets for managing neurodegeneration. Curcumin, with multiple special properties, has been effectively prescribed to manage various diseases. It has hepato-protective, anti-carcinogenic, cardio-protective, thrombo-suppressive, anti-inflammatory, chemo-therapeutic, anti-arthritic, chemo-preventive, and anti-oxidant activities. In the current review, the effects of curcumin on astrocytes in common neurodegenerative conditions, such as Huntington’s disease, amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease, are discussed. Hence, it can be concluded that astrocytes play a critical role in neurodegenerative diseases, and curcumin is able to directly modulate astrocyte activity in neurodegenerative diseases.
Graphical Abstract

[1]
Agnello, L.; Ciaccio, M. Neurodegenerative diseases: From molecular basis to therapy. Int. J. Mol. Sci.,  2022, 23(21), 12854.

[2]
Kovacs, G.G.; Budka, H. Current concepts of neuropathological diagnostics in practice: Neurodegenerative diseases. Clin. Neuropathol.,  2010, 29(9), 271-288.
 [http://dx.doi.org/10.5414/NPP29271] [PMID: 20860890]

[3]
Dugger, B.N.; Dickson, D.W. Pathology of neurodegenerative diseases. Cold Spring Harb. Perspect. Biol.,  2017, 9(7), a028035.
 [http://dx.doi.org/10.1101/cshperspect.a028035] [PMID: 28062563]

[4]
Maiti, P.; Manna, J. Dietary curcumin: A potent natural polyphenol for neurodegenerative diseases therapy. MOJ Anat. Physiol.,  2015, 1(5), 127-132.
 [http://dx.doi.org/10.15406/mojap.2015.01.00026]

[5]
Monroy, A.; Lithgow, G.J.; Alavez, S. Curcumin and neurodegenerative diseases. Biofactors,  2013, 39(1), 122-132.
 [http://dx.doi.org/10.1002/biof.1063] [PMID: 23303664]

[6]
Edland, S.D.; Silverman, J.M.; Peskind, E.R.; Tsuang, D.; Wijsman, E.; Morris, J.C. Increased risk of dementia in mothers of Alzheimer’s disease cases. Neurology,  1996, 47(1), 254-256.
 [http://dx.doi.org/10.1212/WNL.47.1.254] [PMID: 8710088]

[7]
Kovacs, G. Current concepts of neurodegenerative diseases. Eur. Med. J. Neurol.,  2014, 1, 78-86.

[8]
Browne, P.; Chandraratna, D.; Angood, C.; Tremlett, H.; Baker, C.; Taylor, B.V.; Thompson, A.J. Atlas of Multiple Sclerosis 2013: A growing global problem with widespread inequity. Neurology,  2014, 83(11), 1022-1024.
 [http://dx.doi.org/10.1212/WNL.0000000000000768] [PMID: 25200713]

[9]
Hroudová, J; Singh, N; Fišar, Z. Mitochondrial dysfunctions in neurodegenerative diseases: Relevance to Alzheimer’s disease. BioMed Res. Int.,  2014, 2014, 175062.

[10]
Reddy, P.H.; Beal, M.F. Amyloid beta, mitochondrial dysfunction and synaptic damage: Implications for cognitive decline in aging and Alzheimer’s disease. Trends Mol. Med.,  2008, 14(2), 45-53.
 [http://dx.doi.org/10.1016/j.molmed.2007.12.002] [PMID: 18218341]

[11]
Rocha, E.M.; De Miranda, B.; Sanders, L.H. Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson’s disease. Neurobiol. Dis.,  2018, 109(Pt B), 249-257.
 [http://dx.doi.org/10.1016/j.nbd.2017.04.004] [PMID: 28400134]

[12]
Niu, J.; Yu, M.; Wang, C.; Xu, Z. Leucine-rich repeat kinase 2 disturbs mitochondrial dynamics via Dynamin-like protein. J. Neurochem.,  2012, 122(3), 650-658.
 [http://dx.doi.org/10.1111/j.1471-4159.2012.07809.x] [PMID: 22639965]

[13]
Dodson, M.W.; Guo, M. Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson’s disease. Curr. Opin. Neurobiol.,  2007, 17(3), 331-337.
 [http://dx.doi.org/10.1016/j.conb.2007.04.010] [PMID: 17499497]

[14]
Song, W.; Chen, J.; Petrilli, A.; Liot, G.; Klinglmayr, E.; Zhou, Y.; Poquiz, P.; Tjong, J.; Pouladi, M.A.; Hayden, M.R.; Masliah, E.; Ellisman, M.; Rouiller, I.; Schwarzenbacher, R.; Bossy, B.; Perkins, G.; Bossy-Wetzel, E. Mutant huntingtin binds the mitochondrial fission GTPase dynamin-related protein-1 and increases its enzymatic activity. Nat. Med.,  2011, 17(3), 377-382.
 [http://dx.doi.org/10.1038/nm.2313] [PMID: 21336284]

[15]
Shin, J.H.; Ko, H.S.; Kang, H.; Lee, Y.; Lee, Y.I.; Pletinkova, O.; Troconso, J.C.; Dawson, V.L.; Dawson, T.M. PARIS (ZNF746) repression of PGC-1α contributes to neurodegeneration in Parkinson’s disease. Cell,  2011, 144(5), 689-702.
 [http://dx.doi.org/10.1016/j.cell.2011.02.010] [PMID: 21376232]

[16]
Barreto, G.E.; Capani, F.; Gonzalez, J.; Morales, L. Role of astrocytes in neurodegenerative diseases; INTECH Open Access Publisher: London, United Kingdom, 2011, pp. 1-19.

[17]
González-Reyes, R.E.; Nava-Mesa, M.O.; Vargas-Sánchez, K.; Ariza-Salamanca, D.; Mora-Muñoz, L. Involvement of astrocytes in Alzheimer’s disease from a neuroinflammatory and oxidative stress perspective. Front. Mol. Neurosci.,  2017, 10, 427.
 [http://dx.doi.org/10.3389/fnmol.2017.00427] [PMID: 29311817]

[18]
Qureshi, M.; Al-Suhaimi, E.A.; Wahid, F.; Shehzad, O.; Shehzad, A. Therapeutic potential of curcumin for multiple sclerosis. Neurol. Sci.,  2018, 39(2), 207-214.
 [PMID: 29079885]

[19]
Lobsiger, C.S.; Cleveland, D.W. Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease. Nat. Neurosci.,  2007, 10(11), 1355-1360.
 [http://dx.doi.org/10.1038/nn1988] [PMID: 17965655]

[20]
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]

[21]
de la Monte, S.M.; Sohn, Y.K.; Ganju, N.; Wands, J.R. P53- and CD95-associated apoptosis in neurodegenerative diseases. Lab. Invest.,  1998, 78(4), 401-411.
 [PMID: 9564885]

[22]
Tatton, W.G.; Olanow, C.W. Apoptosis in neurodegenerative diseases: The role of mitochondria. Biochim. Biophys. Acta Bioenerg.,  1999, 1410(2), 195-213.
 [http://dx.doi.org/10.1016/S0005-2728(98)00167-4] [PMID: 10076027]

[23]
Sherman, M.Y.; Goldberg, A.L. Cellular defenses against unfolded proteins: A cell biologist thinks about neurodegenerative diseases. Neuron,  2001, 29(1), 15-32.
 [http://dx.doi.org/10.1016/S0896-6273(01)00177-5] [PMID: 11182078]

[24]
Reddy, P.H.; Manczak, M.; Yin, X.; Grady, M.C.; Mitchell, A.; Tonk, S.; Kuruva, C.S.; Bhatti, J.S.; Kandimalla, R.; Vijayan, M.; Kumar, S.; Wang, R.; Pradeepkiran, J.A.; Ogunmokun, G.; Thamarai, K.; Quesada, K.; Boles, A.; Reddy, A.P. Protective effects of indian spice curcumin against Amyloid-β in Alzheimer’s disease. J. Alzheimers Dis.,  2018, 61(3), 843-866.
 [http://dx.doi.org/10.3233/JAD-170512] [PMID: 29332042]

[25]
Jabir, N.R.; Khan, F.R.; Tabrez, S. Cholinesterase targeting by polyphenols: A therapeutic approach for the treatment of Alzheimer’s disease. CNS Neurosci. Ther.,  2018, 24(9), 753-762.
 [http://dx.doi.org/10.1111/cns.12971] [PMID: 29770579]

[26]
Sandhir, R.; Yadav, A.; Mehrotra, A.; Sunkaria, A.; Singh, A.; Sharma, S. Curcumin nanoparticles attenuate neurochemical and neurobehavioral deficits in experimental model of Huntington’s disease. Neuromol. Med.,  2014, 16(1), 106-118.
 [http://dx.doi.org/10.1007/s12017-013-8261-y] [PMID: 24008671]

[27]
Chongtham, A.; Agrawal, N. Curcumin modulates cell death and is protective in Huntington’s disease model. Sci. Rep.,  2016, 6(1), 18736.
 [http://dx.doi.org/10.1038/srep18736] [PMID: 26728250]

[28]
Agrawal, S.S.; Gullaiya, S.; Dubey, V.; Singh, V.; Kumar, A.; Nagar, A. Neurodegenerative shielding by curcumin and its derivatives on brain lesions induced by 6-OHDA model of Parkinson’s disease in albino wistar rats. Cardiovasc. Psychiatry Neurol.,  2012, 2012, 942981.

[29]
Stefanis, L. α-Synuclein in Parkinson’s disease. Cold Spring Harb. Perspect. Med.,  2012, 2(2), a009399.
 [http://dx.doi.org/10.1101/cshperspect.a009399] [PMID: 22355802]

[30]
Maiti, P.; Dunbar, G. Use of curcumin, a natural polyphenol for targeting molecular pathways in treating age-related neurodegenerative diseases. Int. J. Mol. Sci.,  2018, 19(6), 1637.
 [http://dx.doi.org/10.3390/ijms19061637] [PMID: 29857538]

[31]
Baecher-Allan, C.; Kaskow, B.J.; Weiner, H.L. Multiple sclerosis: Mechanisms and immunotherapy. Neuron,  2018, 97(4), 742-768.
 [http://dx.doi.org/10.1016/j.neuron.2018.01.021] [PMID: 29470968]

[32]
Ponath, G.; Park, C.; Pitt, D. The role of astrocytes in multiple sclerosis. Front. Immunol.,  2018, 9, 217.
 [http://dx.doi.org/10.3389/fimmu.2018.00217] [PMID: 29515568]

[33]
Seyedzadeh, M.H.; Safari, Z.; Zare, A.; Gholizadeh Navashenaq, J.; Razavi, A.; Kardar, G.A.; Khorramizadeh, M.R. Study of curcumin immunomodulatory effects on reactive astrocyte cell function. Int. Immunopharmacol.,  2014, 22(1), 230-235.
 [http://dx.doi.org/10.1016/j.intimp.2014.06.035] [PMID: 24998635]

[34]
Suksuphew, S.; Noisa, P. Neural stem cells could serve as a therapeutic material for age-related neurodegenerative diseases. World J. Stem Cells,  2015, 7(2), 502-511.
 [http://dx.doi.org/10.4252/wjsc.v7.i2.502] [PMID: 25815135]

[35]
Bedlack, R. ALSUntangled 44: curcumin. Amyotroph. Lateral Scler. Frontotemporal Degener.,  2018, 19(7-8), 623-629.
 [http://dx.doi.org/10.1080/21678421.2018.1440738] [PMID: 29493344]

[36]
Jukkola, P.; Guerrero, T.; Gray, V.; Gu, C. Astrocytes differentially respond to inflammatory autoimmune insults and imbalances of neural activity. Acta Neuropathol. Commun.,  2013, 1(1), 70.
 [http://dx.doi.org/10.1186/2051-5960-1-70] [PMID: 24252623]

[37]
Claycomb, K.; Johnson, K.; Winokur, P.; Sacino, A.; Crocker, S. Astrocyte regulation of CNS inflammation and remyelination. Brain Sci.,  2013, 3(4), 1109-1127.
 [http://dx.doi.org/10.3390/brainsci3031109] [PMID: 24961523]

[38]
Maragakis, N.J.; Rothstein, J.D. Mechanisms of Disease: Astrocytes in neurodegenerative disease. Nat. Clin. Pract. Neurol.,  2006, 2(12), 679-689.
 [http://dx.doi.org/10.1038/ncpneuro0355] [PMID: 17117171]

[39]
Molofsky, A.V.; Krenick, R.; Ullian, E.; Tsai, H.; Deneen, B.; Richardson, W.D.; Barres, B.A.; Rowitch, D.H. Astrocytes and disease: A neurodevelopmental perspective. Genes Dev.,  2012, 26(9), 891-907.
 [http://dx.doi.org/10.1101/gad.188326.112] [PMID: 22549954]

[40]
Sofroniew, M.V.; Vinters, H.V. Astrocytes: Biology and pathology. Acta Neuropathol.,  2010, 119(1), 7-35.
 [http://dx.doi.org/10.1007/s00401-009-0619-8] [PMID: 20012068]

[41]
Ransohoff, R.M.; Engelhardt, B. The anatomical and cellular basis of immune surveillance in the central nervous system. Nat. Rev. Immunol.,  2012, 12(9), 623-635.
 [http://dx.doi.org/10.1038/nri3265] [PMID: 22903150]

[42]
Schumacher, M.; Hussain, R.; Gago, N.; Oudinet, J.P.; Mattern, C.; Ghoumari, A.M. Progesterone synthesis in the nervous system: Implications for myelination and myelin repair. Front. Neurosci.,  2012, 6, 10.
 [http://dx.doi.org/10.3389/fnins.2012.00010] [PMID: 22347156]

[43]
Voskuhl, R.R.; Peterson, R.S.; Song, B.; Ao, Y.; Morales, L.B.J.; Tiwari-Woodruff, S.; Sofroniew, M.V. Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS. J. Neurosci.,  2009, 29(37), 11511-11522.
 [http://dx.doi.org/10.1523/JNEUROSCI.1514-09.2009] [PMID: 19759299]

[44]
Toft-Hansen, H.; Füchtbauer, L.; Owens, T. Inhibition of reactive astrocytosis in established experimental autoimmune encephalomyelitis favors infiltration by myeloid cells over T cells and enhances severity of disease. Glia,  2011, 59(1), 166-176.
 [http://dx.doi.org/10.1002/glia.21088] [PMID: 21046558]

[45]
Nair, A.; Frederick, T.J.; Miller, S.D. Astrocytes in multiple sclerosis: A product of their environment. Cell. Mol. Life Sci.,  2008, 65(17), 2702-2720.
 [http://dx.doi.org/10.1007/s00018-008-8059-5] [PMID: 18516496]

[46]
Wang, X.; Haroon, F.; Karray, S. Martina Deckert; Schlüter, D. Astrocytic Fas ligand expression is required to induce T-cell apoptosis and recovery from experimental autoimmune encephalomyelitis. Eur. J. Immunol.,  2013, 43(1), 115-124.
 [http://dx.doi.org/10.1002/eji.201242679] [PMID: 23011975]

[47]
Dong, Y.; Benveniste, E.N. Immune function of astrocytes. Glia,  2001, 36(2), 180-190.
 [http://dx.doi.org/10.1002/glia.1107] [PMID: 11596126]

[48]
Soos, J.M.; Ashley, T.A.; Morrow, J.; Patarroyo, J.C.; Szente, B.E.; Zamvil, S.S. Differential expression of B7 co-stimulatory molecules by astrocytes correlates with T cell activation and cytokine production. Int. Immunol.,  1999, 11(7), 1169-1179.
 [http://dx.doi.org/10.1093/intimm/11.7.1169] [PMID: 10383950]

[49]
Girvin, A.M.; Gordon, K.B.; Welsh, C.J.; Clipstone, N.A.; Miller, S.D. Differential abilities of central nervous system resident endothelial cells and astrocytes to serve as inducible antigen-presenting cells. Blood,  2002, 99(10), 3692-3701.
 [http://dx.doi.org/10.1182/blood-2001-12-0229] [PMID: 11986225]

[50]
Ambegaokar, S.S.; Wu, L.; Alamshahi, K.; Lau, J.; Jazayeri, L.; Chan, S.; Khanna, P.; Hsieh, E.; Timiras, P.S. Curcumin inhibits dose-dependently and time-dependently neuroglial cell proliferation and growth. Neuroendocrinol. Lett.,  2003, 24(6), 469-473.
 [PMID: 15073579]

[51]
Saas, P.; Boucraut, J.; Quiquerez, A.L.; Schnuriger, V.; Perrin, G.; Desplat-Jego, S.; Bernard, D.; Walker, P.R.; Dietrich, P.Y. CD95 (Fas/Apo-1) as a receptor governing astrocyte apoptotic or inflammatory responses: A key role in brain inflammation? J. Immunol.,  1999, 162(4), 2326-2333.
 [http://dx.doi.org/10.4049/jimmunol.162.4.2326] [PMID: 9973511]

[52]
Farhood, B.; Najafi, M.; Talakesh, T.; Tabatabaee, N.; Atoof, F.; Aliasgharzadeh, A.; Sarvizade, M. Effect of nano-curcumin on radiotherapy-induced skin reaction in breast cancer patients: A randomized, triple-blind, placebo-controlled trial. Curr. Radiopharm.,  2022, 15(4), 332-340.
 [http://dx.doi.org/10.2174/1874471015666220623104316] [PMID: 35747962]

[53]
Moutabian, H.; Ghahramani-Asl, R.; Mortezazadeh, T.; Laripour, R.; Narmani, A.; Zamani, H.; Ataei, G.; Bagheri, H.; Farhood, B.; Sathyapalan, T.; Sahebkar, A. The cardioprotective effects of nano‐curcumin against doxorubicin‐induced cardiotoxicity: A systematic review. Biofactors,  2022, 48(3), 597-610.
 [http://dx.doi.org/10.1002/biof.1823] [PMID: 35080781]

[54]
Najafi, M.; Mortezaee, K.; Rahimifard, M.; Farhood, B.; Haghi-Aminjan, H. The role of curcumin/curcuminoids during gastric cancer chemotherapy: A systematic review of non-clinical study. Life Sci.,  2020, 257, 118051.
 [http://dx.doi.org/10.1016/j.lfs.2020.118051] [PMID: 32634426]

[55]
Jurenka, J.S.; Jurenka, M. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: A review of preclinical and clinical research. Altern. Med. Rev.,  2009, 14(2), 141-153.
 [PMID: 19594223]

[56]
Okamoto, Y.; Tanaka, M.; Fukui, T.; Masuzawa, T. Inhibition of interleukin 17 production by curcumin in mice with collagen-induced arthritis. Biomed. Res.,  2011, 22(3), 299-304.

[57]
Srivastava, R.M.; Singh, S.; Dubey, S.K.; Misra, K.; Khar, A. Immunomodulatory and therapeutic activity of curcumin. Int. Immunopharmacol.,  2011, 11(3), 331-341.
 [http://dx.doi.org/10.1016/j.intimp.2010.08.014] [PMID: 20828642]

[58]
Mortezaee, K.; Salehi, E.; Mirtavoos-mahyari, H.; Motevaseli, E.; Najafi, M.; Farhood, B.; Rosengren, R.J.; Sahebkar, A. Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy. J. Cell. Physiol.,  2019, 234(8), 12537-12550.
 [http://dx.doi.org/10.1002/jcp.28122] [PMID: 30623450]

[59]
Farhood, B.; Mortezaee, K.; Goradel, N.H.; Khanlarkhani, N.; Salehi, E.; Nashtaei, M.S.; Najafi, M.; Sahebkar, A. Curcumin as an anti‐inflammatory agent: Implications to radiotherapy and chemotherapy. J. Cell. Physiol.,  2019, 234(5), 5728-5740.
 [http://dx.doi.org/10.1002/jcp.27442] [PMID: 30317564]

[60]
Ghanbarzadeh, A.; Farhood, B.; Noodeh, F.A.; Mosaed, R.; Hassanzadeh, G.; Bagheri, H.; Najafi, M. Histopathological evaluation of nanocurcumin for mitigation of radiation-induced small intestine injury. Curr. Radiopharm.,  2023, 16(1), 57-63.

[61]
Mishra, S.; Palanivelu, K. The effect of curcumin (turmeric) on Alzheimer′s disease: An overview. Ann. Indian Acad. Neurol.,  2008, 11(1), 13-19.
 [http://dx.doi.org/10.4103/0972-2327.40220] [PMID: 19966973]

[62]
Huang, N.; Lu, S.; Liu, X.G.; Zhu, J.; Wang, Y.J.; Liu, R.T. PLGA nanoparticles modified with a BBB-penetrating peptide co-delivering Aβ generation inhibitor and curcumin attenuate memory deficits and neuropathology in Alzheimer’s disease mice. Oncotarget,  2017, 8(46), 81001-81013.
 [http://dx.doi.org/10.18632/oncotarget.20944] [PMID: 29113362]

[63]
Meng, F.; Asghar, S.; Gao, S.; Su, Z.; Song, J.; Huo, M.; Meng, W.; Ping, Q.; Xiao, Y. A novel LDL-mimic nanocarrier for the targeted delivery of curcumin into the brain to treat Alzheimer’s disease. Colloids Surf. B Biointerfaces,  2015, 134, 88-97.
 [http://dx.doi.org/10.1016/j.colsurfb.2015.06.025] [PMID: 26162977]

[64]
Cheng, K.K.; Chan, P.S.; Fan, S.; Kwan, S.M.; Yeung, K.L. Wáng, Y.X.J.; Chow, A.H.L.; Wu, E.X.; Baum, L. Curcumin-conjugated magnetic nanoparticles for detecting amyloid plaques in Alzheimer’s disease mice using magnetic resonance imaging (MRI). Biomaterials,  2015, 44, 155-172.
 [http://dx.doi.org/10.1016/j.biomaterials.2014.12.005] [PMID: 25617135]

[65]
Zhang, N.; Yan, F.; Liang, X.; Wu, M.; Shen, Y.; Chen, M.; Xu, Y.; Zou, G.; Jiang, P.; Tang, C.; Zheng, H.; Dai, Z. Localized delivery of curcumin into brain with polysorbate 80-modified cerasomes by ultrasound-targeted microbubble destruction for improved Parkinson’s disease therapy. Theranostics,  2018, 8(8), 2264-2277.
 [http://dx.doi.org/10.7150/thno.23734] [PMID: 29721078]

[66]
Siddique, Y.H.; Khan, W.; Singh, B.R.; Naqvi, A.H. Synthesis of alginate-curcumin nanocomposite and its protective role in transgenic Drosophila model of Parkinson’s disease. ISRN Pharmacol.,  2013, 2013, 1-8.
 [http://dx.doi.org/10.1155/2013/794582] [PMID: 24171120]

[67]
Desai, P.P.; Patravale, V.B. Curcumin cocrystal micelles-multifunctional nanocomposites for management of neurodegenerative ailments. J. Pharm. Sci.,  2018, 107(4), 1143-1156.
 [http://dx.doi.org/10.1016/j.xphs.2017.11.014] [PMID: 29183742]

[68]
McClure, R.; Ong, H.; Janve, V.; Barton, S.; Zhu, M.; Li, B.; Dawes, M.; Jerome, W.G.; Anderson, A.; Massion, P.; Gore, J.C.; Pham, W. Aerosol Delivery of curcumin reduced Amyloid-β deposition and improved cognitive performance in a transgenic model of Alzheimer’s Disease. J. Alzheimers Dis.,  2016, 55(2), 797-811.
 [http://dx.doi.org/10.3233/JAD-160289] [PMID: 27802223]

[69]
Kimura, K.; Teranishi, S.; Fukuda, K.; Kawamoto, K.; Nishida, T. Delayed disruption of barrier function in cultured human corneal epithelial cells induced by tumor necrosis factor-α in a manner dependent on NF-kappaB. Invest. Ophthalmol. Vis. Sci.,  2008, 49(2), 565-571.
 [http://dx.doi.org/10.1167/iovs.07-0419] [PMID: 18235000]

[70]
Xie, L.; Li, X.K.; Takahara, S. Curcumin has bright prospects for the treatment of multiple sclerosis. Int. Immunopharmacol.,  2011, 11(3), 323-330.
 [http://dx.doi.org/10.1016/j.intimp.2010.08.013] [PMID: 20828641]

[71]
Wang, Y.J.; Pan, M.H.; Cheng, A.L.; Lin, L.I.; Ho, Y.S.; Hsieh, C.Y.; Lin, J.K. Stability of curcumin in buffer solutions and characterization of its degradation products. J. Pharm. Biomed. Anal.,  1997, 15(12), 1867-1876.
 [http://dx.doi.org/10.1016/S0731-7085(96)02024-9] [PMID: 9278892]

[72]
Ireson, C.; Orr, S.; Jones, D.J.; Verschoyle, R.; Lim, C-K.; Luo, J-L.; Howells, L.; Plummer, S.; Jukes, R.; Williams, M.; Steward, W.P.; Gescher, A. Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Res.,  2001, 61(3), 1058-1064.
 [PMID: 11221833]

[73]
Yallapu, M.M.; Jaggi, M.; Chauhan, S.C. Curcumin nanoformulations: A future nanomedicine for cancer. Drug Discov. Today,  2012, 17(1-2), 71-80.
 [http://dx.doi.org/10.1016/j.drudis.2011.09.009] [PMID: 21959306]

[74]
Overchuk, M.; Zheng, G. Overcoming obstacles in the tumor microenvironment: Recent advancements in nanoparticle delivery for cancer theranostics. Biomaterials,  2017, 156, 217-237.
 [PMID: 29207323]

[75]
Ding, T.; Li, T.; Li, J. Impact of curcumin liposomes with anti-quorum sensing properties against foodborne pathogens Aeromonas hydrophila and Serratia grimesii. Microb. Pathog.,  2018, 122, 137-143.
 [http://dx.doi.org/10.1016/j.micpath.2018.06.009] [PMID: 29885365]

[76]
Hasan, M.; Latifi, S.; Kahn, C.; Tamayol, A.; Habibey, R.; Passeri, E.; Linder, M.; Arab-Tehrany, E. The positive role of curcumin-loaded salmon nanoliposomes on the culture of primary cortical neurons. Mar. Drugs,  2018, 16(7), 218.
 [http://dx.doi.org/10.3390/md16070218] [PMID: 29941790]

[77]
Liu, W.; Zhai, Y.; Heng, X.; Che, F.Y.; Chen, W.; Sun, D.; Zhai, G. Oral bioavailability of curcumin: Problems and advancements. J. Drug Target.,  2016, 24(8), 694-702.
 [http://dx.doi.org/10.3109/1061186X.2016.1157883] [PMID: 26942997]

[78]
Karlstetter, M.; Lippe, E.; Walczak, Y.; Moehle, C.; Aslanidis, A.; Mirza, M.; Langmann, T. Curcumin is a potent modulator of microglial gene expression and migration. J. Neuroinflammation,  2011, 8(1), 125.
 [http://dx.doi.org/10.1186/1742-2094-8-125] [PMID: 21958395]

[79]
Anand, P.; Thomas, S.G.; Kunnumakkara, A.B.; Sundaram, C.; Harikumar, K.B.; Sung, B.; Tharakan, S.T.; Misra, K.; Priyadarsini, I.K.; Rajasekharan, K.N.; Aggarwal, B.B. Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem. Pharmacol.,  2008, 76(11), 1590-1611.
 [http://dx.doi.org/10.1016/j.bcp.2008.08.008] [PMID: 18775680]

[80]
Natarajan, C.; Bright, J.J. Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes. J. Immunol.,  2002, 168(12), 6506-6513.
 [http://dx.doi.org/10.4049/jimmunol.168.12.6506] [PMID: 12055272]

[81]
Ye, J.; Zhang, Y. Curcumin protects against intracellular amyloid toxicity in rat primary neurons. Int. J. Clin. Exp. Med.,  2012, 5(1), 44-49.
 [PMID: 22328947]

[82]
Lavoie, S.; Chen, Y.; Dalton, T.P.; Gysin, R.; Cuénod, M.; Steullet, P.; Do, K.Q. Curcumin, quercetin, and tBHQ modulate glutathione levels in astrocytes and neurons: Importance of the glutamate cysteine ligase modifier subunit. J. Neurochem.,  2009, 108(6), 1410-1422.
 [http://dx.doi.org/10.1111/j.1471-4159.2009.05908.x] [PMID: 19183254]

[83]
Wang, J.; Zhang, Y.J.; Du, S. The protective effect of curcumin on Aβ induced aberrant cell cycle reentry on primary cultured rat cortical neurons. Eur. Rev. Med. Pharmacol. Sci.,  2012, 16(4), 445-454.
 [PMID: 22696871]

[84]
Ortiz-Ortiz, M.A. Morán, J.M.; Ruiz-Mesa, L.M.; Niso-Santano, M.; Bravo-SanPedro, J.M.; Gَmez-Sánchez, R.; González-Polo, R.A.; Fuentes, J.M. Curcumin exposure induces expression of the Parkinson’s disease-associated leucine-rich repeat kinase 2 (LRRK2) in rat mesencephalic cells. Neurosci. Lett.,  2010, 468(2), 120-124.
 [http://dx.doi.org/10.1016/j.neulet.2009.10.081] [PMID: 19879924]

[85]
Jiang, H.; Tian, X.; Guo, Y.; Duan, W.; Bu, H.; Li, C. Activation of nuclear factor erythroid 2-related factor 2 cytoprotective signaling by curcumin protect primary spinal cord astrocytes against oxidative toxicity. Biol. Pharm. Bull.,  2011, 34(8), 1194-1197.
 [http://dx.doi.org/10.1248/bpb.34.1194] [PMID: 21804205]

[86]
Rogers, N.M.; Kireta, S.; Coates, P.T.H. Curcumin induces maturation-arrested dendritic cells that expand regulatory T cells in vitro and in vivo. Clin. Exp. Immunol.,  2010, 162(3), 460-473.
 [http://dx.doi.org/10.1111/j.1365-2249.2010.04232.x] [PMID: 21070208]

[87]
Cong, Y.; Wang, L.; Konrad, A.; Schoeb, T.; Elson, C.O. Curcumin induces the tolerogenic dendritic cell that promotes differentiation of intestine-protective regulatory T cells. Eur. J. Immunol.,  2009, 39(11), 3134-3146.
 [http://dx.doi.org/10.1002/eji.200939052] [PMID: 19839007]

[88]
Fahey, A.J.; Adrian Robins, R.; Constantinescu, C.S. Curcumin modulation of IFN-β and IL-12 signalling and cytokine induction in human T cells. J. Cell. Mol. Med.,  2007, 11(5), 1129-1137.
 [http://dx.doi.org/10.1111/j.1582-4934.2007.00089.x] [PMID: 17979888]

[89]
Forward, N.A.; Conrad, D.M.; Power Coombs, M.R.; Doucette, C.D.; Furlong, S.J.; Lin, T.J.; Hoskin, D.W. Curcumin blocks interleukin (IL)-2 signaling in T-lymphocytes by inhibiting IL-2 synthesis, CD25 expression, and IL-2 receptor signaling. Biochem. Biophys. Res. Commun.,  2011, 407(4), 801-806.
 [http://dx.doi.org/10.1016/j.bbrc.2011.03.103] [PMID: 21443863]

[90]
Ranjan, D.; Chen, C.; Johnston, T.D.; Jeon, H.; Nagabhushan, M. Curcumin inhibits mitogen stimulated lymphocyte proliferation, NFκB activation, and IL-2 signaling. J. Surg. Res.,  2004, 121(2), 171-177.
 [http://dx.doi.org/10.1016/j.jss.2004.04.004] [PMID: 15501456]

[91]
Jagetia, G.C.; Aggarwal, B.B. “Spicing up” of the immune system by curcumin. J. Clin. Immunol.,  2007, 27(1), 19-35.
 [http://dx.doi.org/10.1007/s10875-006-9066-7] [PMID: 17211725]

[92]
Aggarwal, B.B.; Sung, B. Pharmacological basis for the role of curcumin in chronic diseases: An age-old spice with modern targets. Trends Pharmacol. Sci.,  2009, 30(2), 85-94.
 [http://dx.doi.org/10.1016/j.tips.2008.11.002] [PMID: 19110321]

[93]
Ortiz, G.G.; Pacheco-Moisés, F.P. Macías-Islas, M.Á.; Flores-Alvarado, L.J.; Mireles-Ramírez, M.A.; González-Renovato, E.D.; Hernández-Navarro, V.E.; Sánchez-Lَpez, A.L.; Alatorre-Jiménez, M.A. Role of the blood-brain barrier in multiple sclerosis. Arch. Med. Res.,  2014, 45(8), 687-697.
 [http://dx.doi.org/10.1016/j.arcmed.2014.11.013] [PMID: 25431839]

[94]
Aggarwal, B.B.; Harikumar, K.B. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int. J. Biochem. Cell Biol.,  2009, 41(1), 40-59.
 [http://dx.doi.org/10.1016/j.biocel.2008.06.010] [PMID: 18662800]

[95]
Hatcher, H.; Planalp, R.; Cho, J.; Torti, F.M.; Torti, S.V. Curcumin: From ancient medicine to current clinical trials. Cell. Mol. Life Sci.,  2008, 65(11), 1631-1652.
 [http://dx.doi.org/10.1007/s00018-008-7452-4] [PMID: 18324353]

[96]
Trist, B.G.; Hare, D.J.; Double, K.L. Oxidative stress in the aging substantia nigra and the etiology of Parkinson’s disease. Aging Cell,  2019, 18(6), e13031.
 [http://dx.doi.org/10.1111/acel.13031] [PMID: 31432604]

[97]
Ak, T. Gülçin, İ. Antioxidant and radical scavenging properties of curcumin. Chem. Biol. Interact.,  2008, 174(1), 27-37.
 [http://dx.doi.org/10.1016/j.cbi.2008.05.003] [PMID: 18547552]

[98]
Carroll, R.E.; Benya, R.V.; Turgeon, D.K.; Vareed, S.; Neuman, M.; Rodriguez, L.; Kakarala, M.; Carpenter, P.M.; McLaren, C.; Meyskens, F.L., Jr; Brenner, D.E. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev. Res.,  2011, 4(3), 354-364.
 [http://dx.doi.org/10.1158/1940-6207.CAPR-10-0098] [PMID: 21372035]

[99]
Wang, J.; Du, X.X.; Jiang, H.; Xie, J.X. Curcumin attenuates 6-hydroxydopamine-induced cytotoxicity by anti-oxidation and nuclear factor-kappaB modulation in MES23.5 cells. Biochem. Pharmacol.,  2009, 78(2), 178-183.
 [http://dx.doi.org/10.1016/j.bcp.2009.03.031] [PMID: 19464433]

[100]
Xiong, Z.; Hongmei, Z.; Lu, S.; Yu, L. Curcumin mediates presenilin-1 activity to reduce β-amyloid production in a model of Alzheimer’s disease. Pharmacol. Rep.,  2011, 63(5), 1101-1108.
 [http://dx.doi.org/10.1016/S1734-1140(11)70629-6] [PMID: 22180352]

[101]
Sever, B. Türkeş C.; Altıntop, M.D.; Demir, Y.; Akalın اiftçi, G.; Beydemir, Ş. Novel metabolic enzyme inhibitors designed through the molecular hybridization of thiazole and pyrazoline scaffolds. Arch. Pharm.,  2021, 354(12), 2100294.
 [http://dx.doi.org/10.1002/ardp.202100294] [PMID: 34569655]

[102]
Oztaskin, N.; Goksu, S.; Demir, Y.; Maras, A. Gulcin, İ. Synthesis of novel bromophenol with diaryl methanes-determination of their inhibition effects on carbonic anhydrase and acetylcholinesterase. Molecules,  2022, 27(21), 7426.
 [http://dx.doi.org/10.3390/molecules27217426] [PMID: 36364255]

[103]
Aktaş A.; Yakalı G.; Demir, Y.; Gülçin, İ.; Aygün, M.; Gِk, Y. The palladium-based complexes bearing 1, 3-dibenzylbenzimi-dazolium with morpholine, triphenylphosphine, and pyridine derivate ligands: Synthesis, characterization, structure and enzyme inhibitions. Heliyon,  2022, 8(9), e10625.
 [http://dx.doi.org/10.1016/j.heliyon.2022.e10625] [PMID: 36185151]

[104]
Hewlings, S.; Kalman, D. Curcumin: A review of its’ effects on human health. Foods,  2017, 6(10), 92.
 [http://dx.doi.org/10.3390/foods6100092] [PMID: 29065496]

[105]
Wang, H.Y. Lee, D.H.S.; D’Andrea, M.R.; Peterson, P.A.; Shank, R.P.; Reitz, A.B. β-Amyloid(1-42) binds to α7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer’s disease pathology. J. Biol. Chem.,  2000, 275(8), 5626-5632.
 [http://dx.doi.org/10.1074/jbc.275.8.5626] [PMID: 10681545]

[106]
Mahmudov, I.; Demir, Y.; Sert, Y.; Abdullayev, Y.; Sujayev, A.; Alwasel, S.H.; Gulcin, I. Synthesis and inhibition profiles of N-benzyl- and N-allyl aniline derivatives against carbonic anhydrase and acetylcholinesterase – A molecular docking study. Arab. J. Chem.,  2022, 15(3), 103645.
 [http://dx.doi.org/10.1016/j.arabjc.2021.103645]

[107]
Güleç, Ö.; Türkeş, C.; Arslan, M.; Demir, Y.; Yeni, Y.; Hacımüftüoğlu, A.; Ereminsoy, E.; Küfrevioğlu, Ö.İ.; Beydemir, Ş. Cytotoxic effect, enzyme inhibition, and in silico studies of some novel N-substituted sulfonyl amides incorporating 1,3,4-oxadiazol structural motif. Mol. Divers.,  2022, 26(5), 2825-2845.
 [http://dx.doi.org/10.1007/s11030-022-10422-8] [PMID: 35397086]

[108]
Yiğit, M.; Demir, Y.; Barut Celepci, D.; Taskin-Tok, T.; Arınç, A.; Yiğit, B.; Aygün, M.; Özdemir, İ.; Gülçin, İ. Phthalimide‐tethered imidazolium salts: Synthesis, characterization, enzyme inhibitory properties, and in silico studies. Arch. Pharm. (Weinheim),  2022, 355(12), 2200348.
 [http://dx.doi.org/10.1002/ardp.202200348] [PMID: 36153848]

[109]
Tai, Y.H.; Lin, Y.Y.; Wang, K.C.; Chang, C.L.; Chen, R.Y.; Wu, C.C.; Cheng, I.H. Curcuminoid submicron particle ameliorates cognitive deficits and decreases amyloid pathology in Alzheimer’s disease mouse model. Oncotarget,  2018, 9(12), 10681-10697.
 [http://dx.doi.org/10.18632/oncotarget.24369] [PMID: 29535835]

[110]
Koistinaho, M.; Lin, S.; Wu, X.; Esterman, M.; Koger, D.; Hanson, J.; Higgs, R.; Liu, F.; Malkani, S.; Bales, K.R.; Paul, S.M. Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides. Nat. Med.,  2004, 10(7), 719-726.
 [http://dx.doi.org/10.1038/nm1058] [PMID: 15195085]

[111]
Pihlaja, R.; Koistinaho, J.; Kauppinen, R.; Sandholm, J.; Tanila, H.; Koistinaho, M. Multiple cellular and molecular mechanisms Are involved in human Aβ clearance by transplanted adult astrocytes. Glia,  2011, 59(11), 1643-1657.
 [http://dx.doi.org/10.1002/glia.21212] [PMID: 21826742]

[112]
Ries, M.; Sastre, M. Mechanisms of Aβ clearance and degradation by glial cells. Front. Aging Neurosci.,  2016, 8, 160.
 [http://dx.doi.org/10.3389/fnagi.2016.00160] [PMID: 27458370]

[113]
Lim, G.P.; Chu, T.; Yang, F.; Beech, W.; Frautschy, S.A.; Cole, G.M. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J. Neurosci.,  2001, 21(21), 8370-8377.
 [http://dx.doi.org/10.1523/JNEUROSCI.21-21-08370.2001] [PMID: 11606625]

[114]
Wang, Y.; Yin, H.; Wang, L.; Shuboy, A.; Lou, J.; Han, B.; Zhang, X.; Li, J. Curcumin as a potential treatment for Alzheimer’s disease: A study of the effects of curcumin on hippocampal expression of glial fibrillary acidic protein. Am. J. Chin. Med.,  2013, 41(1), 59-70.
 [http://dx.doi.org/10.1142/S0192415X13500055] [PMID: 23336507]

[115]
McMillan, L.E.; Brown, J.T.; Henley, J.M.; Cimarosti, H. Profiles of SUMO and ubiquitin conjugation in an Alzheimer’s disease model. Neurosci. Lett.,  2011, 502(3), 201-208.
 [http://dx.doi.org/10.1016/j.neulet.2011.07.045] [PMID: 21843595]

[116]
Zhang, Y.Q.; Sarge, K.D. Sumoylation of amyloid precursor protein negatively regulates Aβ aggregate levels. Biochem. Biophys. Res. Commun.,  2008, 374(4), 673-678.
 [http://dx.doi.org/10.1016/j.bbrc.2008.07.109] [PMID: 18675254]

[117]
Hoppe, J.B.; Rattray, M.; Tu, H.; Salbego, C.G.; Cimarosti, H. SUMO-1 conjugation blocks beta-amyloid-induced astrocyte reactivity. Neurosci. Lett.,  2013, 546, 51-56.
 [http://dx.doi.org/10.1016/j.neulet.2013.04.050] [PMID: 23651519]

[118]
Wang, H.M.; Zhao, Y.X.; Zhang, S.; Liu, G.D.; Kang, W.Y.; Tang, H.D.; Ding, J.Q.; Chen, S.D. PPARgamma agonist curcumin reduces the amyloid-β-stimulated inflammatory responses in primary astrocytes. J. Alzheimers Dis.,  2010, 20(4), 1189-1199.
 [http://dx.doi.org/10.3233/JAD-2010-091336] [PMID: 20413894]

[119]
Strimpakos, A.S.; Sharma, R.A. Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid. Redox Signal.,  2008, 10(3), 511-546.
 [http://dx.doi.org/10.1089/ars.2007.1769] [PMID: 18370854]

[120]
Yang, F.; Lim, G.P.; Begum, A.N.; Ubeda, O.J.; Simmons, M.R.; Ambegaokar, S.S.; Chen, P.P.; Kayed, R.; Glabe, C.G.; Frautschy, S.A.; Cole, G.M. Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J. Biol. Chem.,  2005, 280(7), 5892-5901.
 [http://dx.doi.org/10.1074/jbc.M404751200] [PMID: 15590663]

[121]
Zhang, C.; Browne, A.; Child, D.; Tanzi, R.E. Curcumin decreases amyloid-β peptide levels by attenuating the maturation of amyloid-β precursor protein. J. Biol. Chem.,  2010, 285(37), 28472-28480.
 [http://dx.doi.org/10.1074/jbc.M110.133520] [PMID: 20622013]

[122]
Rogers, J.T.; Randall, J.D.; Eder, P.S.; Huang, X.; Bush, A.I.; Tanzi, R.E.; Venti, A.; Payton, S.M.; Giordano, T.; Nagano, S.; Cahill, C.M.; Moir, R.; Lahiri, D.K.; Greig, N.; Sarang, S.S.; Gullans, S.R. Alzheimer’s disease drug discovery targeted to the APP mRNA 5′Untranslated region. J. Mol. Neurosci.,  2002, 19(1-2), 77-82.
 [http://dx.doi.org/10.1007/s12031-002-0014-6] [PMID: 12212798]

[123]
Uversky, V.N.; Li, J.; Souillac, P.; Millett, I.S.; Doniach, S.; Jakes, R.; Goedert, M.; Fink, A.L. Biophysical properties of the synucleins and their propensities to fibrillate: inhibition of alpha-synuclein assembly by beta- and gamma-synucleins. J. Biol. Chem.,  2002, 277(14), 11970-11978.
 [http://dx.doi.org/10.1074/jbc.M109541200] [PMID: 11812782]

[124]
Klegeris, A. Pelech, S.; Giasson, B.I.; Maguire, J.; Zhang, H.; McGeer, E.G.; McGeer, P.L. α-Synuclein activates stress signaling protein kinases in THP-1 cells and microglia. Neurobiol. Aging,  2008, 29(5), 739-752.
 [http://dx.doi.org/10.1016/j.neurobiolaging.2006.11.013] [PMID: 17166628]

[125]
Klegeris, A.; Giasson, B.I.; Zhang, H.; Maguire, J.; Pelech, S.; McGeer, P.L. Alpha‐synuclein and its disease‐causing mutants induce ICAM‐1 and IL‐6 in human astrocytes and astrocytoma cells. FASEB J.,  2006, 20(12), 2000-2008.
 [http://dx.doi.org/10.1096/fj.06-6183com] [PMID: 17012252]

[126]
Gan, L.; Vargas, M.R.; Johnson, D.A.; Johnson, J.A. Astrocyte-specific overexpression of Nrf2 delays motor pathology and synuclein aggregation throughout the CNS in the alpha-synuclein mutant (A53T) mouse model. J. Neurosci.,  2012, 32(49), 17775-17787.
 [http://dx.doi.org/10.1523/JNEUROSCI.3049-12.2012] [PMID: 23223297]

[127]
Phatnani, H.; Maniatis, T. Astrocytes in neurodegenerative disease. Cold Spring Harb. Perspect. Biol.,  2015, 7(6), a020628.
 [http://dx.doi.org/10.1101/cshperspect.a020628] [PMID: 25877220]

[128]
Saavedra, A.; Baltazar, G.; Santos, P.; Carvalho, C.M.; Duarte, E.P. Selective injury to dopaminergic neurons up-regulates GDNF in substantia nigra postnatal cell cultures: Role of neuron-glia crosstalk. Neurobiol. Dis.,  2006, 23(3), 533-542.
 [http://dx.doi.org/10.1016/j.nbd.2006.04.008] [PMID: 16766196]

[129]
Knott, C.; Stern, G.; Kingsbury, A.; Welcher, A.A.; Wilkin, G.P. Elevated glial brain-derived neurotrophic factor in Parkinson’s diseased nigra. Parkinsonism Relat. Disord.,  2002, 8(5), 329-341.
 [http://dx.doi.org/10.1016/S1353-8020(02)00008-1] [PMID: 15177062]

[130]
Chen, P-S.; Peng, G-S.; Li, G.; Yang, S.; Wu, X.; Wang, C-C.; Wilson, B.; Lu, R-B.; Gean, P-W.; Chuang, D-M.; Hong, J-S. Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes. Mol. Psychiatry,  2006, 11(12), 1116-1125.
 [http://dx.doi.org/10.1038/sj.mp.4001893] [PMID: 16969367]

[131]
Petrova, P.S.; Raibekas, A.; Pevsner, J.; Vigo, N.; Anafi, M.; Moore, M.K.; Peaire, A.E.; Shridhar, V.; Smith, D.I.; Kelly, J.; Durocher, Y.; Commissiong, J.W. MANF: A new mesencephalic, astrocyte-derived neurotrophic factor with selectivity for dopaminergic neurons. J. Mol. Neurosci.,  2003, 20(2), 173-188.
 [http://dx.doi.org/10.1385/JMN:20:2:173] [PMID: 12794311]

[132]
Ishida, Y.; Nagai, A.; Kobayashi, S.; Kim, S.U. Upregulation of protease-activated receptor-1 in astrocytes in Parkinson disease: astrocyte-mediated neuroprotection through increased levels of glutathione peroxidase. J. Neuropathol. Exp. Neurol.,  2006, 65(1), 66-77.
 [http://dx.doi.org/10.1097/01.jnen.0000195941.48033.eb] [PMID: 16410750]

[133]
Cole, G.M.; Teter, B.; Frautschy, S.A. Neuroprotective effects of curcumin. The molecular targets and therapeutic uses of curcumin in health and disease; Springer, 2007, pp. 197-212.
 [http://dx.doi.org/10.1007/978-0-387-46401-5_8]

[134]
Tripanichkul, W.; Jaroensuppaperch, E.O. Ameliorating effects of curcumin on 6-OHDA-induced dopaminergic denervation, glial response, and SOD1 reduction in the striatum of hemiparkinsonian mice. Eur. Rev. Med. Pharmacol. Sci.,  2013, 17(10), 1360-1368.
 [PMID: 23740450]

[135]
Ojha, R.P.; Rastogi, M.; Devi, B.P.; Agrawal, A.; Dubey, G.P. Neuroprotective effect of curcuminoids against inflammation-mediated dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. J. Neuroimmune Pharmacol.,  2012, 7(3), 609-618.
 [http://dx.doi.org/10.1007/s11481-012-9363-2] [PMID: 22527634]

[136]
Chen, J; Tang, XQ; Zhi, JL; Cui, Y; Yu, HM Curcumin protects PC12 cells against 1-methyl-4-phenylpyridinium ioninduced apoptosis by bcl-2-mitochondria-ROS-iNOS pathway. Apoptosis: An Int. J. programmed cell death.,  2006, 11(6), 943-53.

[137]
Yu, S.; Zheng, W.; Xin, N.; Chi, Z.H.; Wang, N.Q.; Nie, Y.X.; Feng, W.Y.; Wang, Z.Y. Curcumin prevents dopaminergic neuronal death through inhibition of the c-Jun N-terminal kinase pathway. Rejuvenation Res.,  2010, 13(1), 55-64.
 [http://dx.doi.org/10.1089/rej.2009.0908] [PMID: 20230279]

[138]
Aoki, E.; Yano, R.; Yokoyama, H.; Kato, H.; Araki, T. Role of nuclear transcription factor kappa B (NF-kappaB) for MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine)-induced apoptosis in nigral neurons of mice. Exp. Mol. Pathol.,  2009, 86(1), 57-64.
 [http://dx.doi.org/10.1016/j.yexmp.2008.10.004] [PMID: 19027004]

[139]
von Geldern, G.; Mowry, E.M. The influence of nutritional factors on the prognosis of multiple sclerosis. Nat. Rev. Neurol.,  2012, 8(12), 678-689.
 [http://dx.doi.org/10.1038/nrneurol.2012.194] [PMID: 23026980]

[140]
Moradi Hasan-Abad, A.; Adabi, E.; Sadroddiny, E.; Khorramizadeh, M.R.; Mazlomi, M.; Mehravar, S.; Kardar, G.A. Functional Deimmunization of Interferon Beta-1b by Identifying and Silencing Human T Cells Epitopes. Iran. J. Allergy Asthma Immunol.,  2019, 18(4), 427-440.
 [http://dx.doi.org/10.18502/ijaai.v18i4.1421] [PMID: 31522451]

[141]
Stephenson, J.; Nutma, E.; van der Valk, P.; Amor, S. Inflammation in CNS neurodegenerative diseases. Immunology,  2018, 154(2), 204-219.
 [http://dx.doi.org/10.1111/imm.12922] [PMID: 29513402]

[142]
Elyaman, W.; Bradshaw, E.M.; Uyttenhove, C.; Dardalhon, V.; Awasthi, A.; Imitola, J.; Bettelli, E.; Oukka, M.; van Snick, J.; Renauld, J.C.; Kuchroo, V.K.; Khoury, S.J. IL-9 induces differentiation of T H 17 cells and enhances function of FoxP3 + natural regulatory T cells. Proc. Natl. Acad. Sci. USA,  2009, 106(31), 12885-12890.
 [http://dx.doi.org/10.1073/pnas.0812530106] [PMID: 19433802]

[143]
Wekerle, H. B cells in multiple sclerosis. Autoimmunity,  2017, 50(1), 57-60.
 [http://dx.doi.org/10.1080/08916934.2017.1281914] [PMID: 28166681]

[144]
Eng, L.F.; Ghirnikar, R.S.; Lee, Y.L. Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000). Neurochem. Res.,  2000, 25(9-10), 1439-1451.
 [http://dx.doi.org/10.1023/A:1007677003387] [PMID: 11059815]

[145]
Chan, W.H.; Wu, H.J.; Hsuuw, Y.D. Curcumin inhibits ROS formation and apoptosis in methylglyoxal-treated human hepatoma G2 cells. Ann. N. Y. Acad. Sci.,  2005, 1042(1), 372-378.
 [http://dx.doi.org/10.1196/annals.1338.057] [PMID: 15965083]

[146]
Ahmed, A.M.; El Fouhil, A.F.; Mohamed, R.A.; Atteya, M.; Abdel-Baky, N.A.; AlRoalle, A.H.; Aldahmash, A.M. Curcumin ameliorates experimental autoimmune acute myocarditis in rats as evidenced by decrease in thioredoxin immunoreactivity. Folia Morphol.,  2015, 74(3), 318-324.
 [http://dx.doi.org/10.5603/FM.2015.0048] [PMID: 26339812]

[147]
Xie, L.; Li, X.K.; Funeshima-Fuji, N.; Kimura, H.; Matsumoto, Y.; Isaka, Y.; Takahara, S. Amelioration of experimental autoimmune encephalomyelitis by curcumin treatment through inhibition of IL-17 production. Int. Immunopharmacol.,  2009, 9(5), 575-581.
 [http://dx.doi.org/10.1016/j.intimp.2009.01.025] [PMID: 19539560]

[148]
Hickey, M.A.; Zhu, C.; Medvedeva, V.; Lerner, R.P.; Patassini, S.; Franich, N.R.; Maiti, P.; Frautschy, S.A.; Zeitlin, S.; Levine, M.S.; Chesselet, M.F. Improvement of neuropathology and transcriptional deficits in CAG 140 knock-in mice supports a beneficial effect of dietary curcumin in Huntington’s disease. Mol. Neurodegener.,  2012, 7(1), 12.
 [http://dx.doi.org/10.1186/1750-1326-7-12] [PMID: 22475209]

[149]
Malik, J.; Choudhary, S.; Kumar, P. Plants and phytochemicals for Huntington′s disease. Pharmacogn. Rev.,  2013, 7(14), 81-91.
 [http://dx.doi.org/10.4103/0973-7847.120505] [PMID: 24347915]

[150]
MacDonald, M.; Ambrose, C.M.; Duyao, M.P.; Myers, R.H.; Lin, C.; Srinidhi, L. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell,  1993, 72(6), 971-983.
 [http://dx.doi.org/10.1016/0092-8674(93)90585-E] [PMID: 8458085]

[151]
Hebb, M.O.; Denovanwright, E.M.; Robertson, H.A. Expression of the Huntington’s disease gene is regulated in astrocytes in the arcuate nucleus of the hypothalamus of postpartum rats. FASEB J.,  1999, 13(9), 1099-1106.
 [http://dx.doi.org/10.1096/fasebj.13.9.1099] [PMID: 10336893]

[152]
Shin, J.Y.; Fang, Z.H.; Yu, Z.X.; Wang, C.E.; Li, S.H.; Li, X.J. Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J. Cell Biol.,  2005, 171(6), 1001-1012.
 [http://dx.doi.org/10.1083/jcb.200508072] [PMID: 16365166]

[153]
Verma, M.; Sharma, A.; Naidu, S.; Bhadra, A.K.; Kukreti, R.; Taneja, V. Curcumin prevents formation of polyglutamine aggregates by inhibiting Vps36, a component of the ESCRT-II complex. PLoS One,  2012, 7(8), e42923.
 [http://dx.doi.org/10.1371/journal.pone.0042923] [PMID: 22880132]

[154]
Raymond, C.K.; Howald-Stevenson, I.; Vater, C.A.; Stevens, T.H. Morphological classification of the yeast vacuolar protein sorting mutants: Evidence for a prevacuolar compartment in class E vps mutants. Mol. Biol. Cell,  1992, 3(12), 1389-1402.
 [http://dx.doi.org/10.1091/mbc.3.12.1389] [PMID: 1493335]

[155]
Bradford, J.; Shin, J.Y.; Roberts, M.; Wang, C.E.; Li, X.J.; Li, S. Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. Proc. Natl. Acad. Sci.,  2009, 106(52), 22480-22485.
 [http://dx.doi.org/10.1073/pnas.0911503106] [PMID: 20018729]

[156]
Ahmadi, M.; Agah, E.; Nafissi, S.; Jaafari, M.R.; Harirchian, M.H.; Sarraf, P.; Faghihi-Kashani, S.; Hosseini, S.J.; Ghoreishi, A.; Aghamollaii, V.; Hosseini, M.; Tafakhori, A. Safety and efficacy of nanocurcumin as add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: A pilot randomized clinical trial. Neurotherapeutics,  2018, 15(2), 430-438.
 [http://dx.doi.org/10.1007/s13311-018-0606-7] [PMID: 29352425]

[157]
Kuraszkiewicz, B. Goszczyńska, H.; Podsiadły-Marczykowska, T.; Piotrkiewicz, M.; Andersen, P.; Gromicho, M.; Grosskreutz, J.; Kuźma-Kozakiewicz, M.; Petri, S.; Stubbendorf, B.; Szacka, K.; Uysal, H.; de Carvalho, M. Potential preventive strategies for amyotrophic lateral sclerosis. Front. Neurosci.,  2020, 14, 428.
 [http://dx.doi.org/10.3389/fnins.2020.00428] [PMID: 32528241]

[158]
Demir, Y. The behaviour of some antihypertension drugs on human serum paraoxonase-1: An important protector enzyme against atherosclerosis. J. Pharm. Pharmacol.,  2019, 71(10), 1576-1583.
 [http://dx.doi.org/10.1111/jphp.13144] [PMID: 31347707]

[159]
Frakes, A.E.; Ferraiuolo, L.; Haidet-Phillips, A.M.; Schmelzer, L.; Braun, L.; Miranda, C.J.; Ladner, K.J.; Bevan, A.K.; Foust, K.D.; Godbout, J.P.; Popovich, P.G.; Guttridge, D.C.; Kaspar, B.K. Microglia induce motor neuron death via the classical NF-κB pathway in amyotrophic lateral sclerosis. Neuron,  2014, 81(5), 1009-1023.
 [http://dx.doi.org/10.1016/j.neuron.2014.01.013] [PMID: 24607225]

[160]
Kahkhaie, K.R.; Mirhosseini, A.; Aliabadi, A.; Mohammadi, A.; Mousavi, M.J.; Haftcheshmeh, S.M.; Sathyapalan, T.; Sahebkar, A. Curcumin: A modulator of inflammatory signaling pathways in the immune system. Inflammopharmacology,  2019, 27(5), 885-900.
 [http://dx.doi.org/10.1007/s10787-019-00607-3] [PMID: 31140036]

[161]
Pajarillo, E.; Rizor, A.; Lee, J.; Aschner, M.; Lee, E. The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: Potential targets for neurotherapeutics. Neuropharmacology,  2019, 161, 107559.
 [http://dx.doi.org/10.1016/j.neuropharm.2019.03.002] [PMID: 30851309]

[162]
Rosenblum, L.T.; Trotti, D. EAAT2 and the molecular signature of amyotrophic lateral sclerosis In: Glial Amino Acid Transporters; , 2017; p. 117-136.
 [http://dx.doi.org/10.1007/978-3-319-55769-4_6]

[163]
Li, L.B.; Toan, S.V.; Zelenaia, O.; Watson, D.J.; Wolfe, J.H.; Rothstein, J.D.; Robinson, M.B. Regulation of astrocytic glutamate transporter expression by Akt: Evidence for a selective transcriptional effect on the GLT-1/EAAT2 subtype. J. Neurochem.,  2006, 97(3), 759-771.
 [http://dx.doi.org/10.1111/j.1471-4159.2006.03743.x] [PMID: 16573655]

[164]
Zhang, Z.; Jiang, M.; Fang, J.; Yang, M.; Zhang, S.; Yin, Y.; Li, D.; Mao, L.; Fu, X.; Hou, Y.; Fu, X.; Fan, C.; Sun, B. Enhanced therapeutic potential of nano-curcumin against subarachnoid hemorrhage-induced blood–brain barrier disruption through inhibition of inflammatory response and oxidative stress. Mol. Neurobiol.,  2017, 54(1), 1-14.
 [http://dx.doi.org/10.1007/s12035-015-9635-y] [PMID: 26708209]

[165]
Demir, Y. Naphthoquinones, benzoquinones, and anthraquinones: Molecular docking, ADME and inhibition studies on human serum paraoxonase‐1 associated with cardiovascular diseases. Drug Dev. Res.,  2020, 81(5), 628-636.
 [http://dx.doi.org/10.1002/ddr.21667] [PMID: 32232985]

[166]
Sangeetha, T.; Chen, Y.; Sasidharan, S. Oxidative stress and aging and medicinal plants as antiaging agents. J. Comple. Med. Res.,  2020, 11(3), 1.
 [http://dx.doi.org/10.5455/jcmr.2020.11.03.01]

[167]
Xavier, J.; Farias, C.P.; Soares, M.S.P. Ayahuasca prevents oxidative stress in a rat model of depression elicited by unpredictable chronic mild stress. Arch. Clin. Psychiatry,  2021, 48, 90-98.

[168]
Bozzo, F.; Mirra, A. Carrى, M.T. Oxidative stress and mitochondrial damage in the pathogenesis of ALS: New perspectives. Neurosci. Lett.,  2017, 636, 3-8.
 [http://dx.doi.org/10.1016/j.neulet.2016.04.065] [PMID: 27150074]

[169]
Blasco, H.; Garcon, G.; Patin, F.; Veyrat-Durebex, C.; Boyer, J.; Devos, D.; Vourc’h, P.; Andres, C.R.; Corcia, P. Panel of oxidative stress and inflammatory biomarkers in ALS: A pilot study. Can. J. Neurol. Sci.,  2017, 44(1), 90-95.
 [http://dx.doi.org/10.1017/cjn.2016.284] [PMID: 27774920]

[170]
Cui, Q.; Li, X.; Zhu, H. Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway. Mol. Med. Rep.,  2016, 13(2), 1381-1388.
 [http://dx.doi.org/10.3892/mmr.2015.4657] [PMID: 26648392]

[171]
Sivandzade, F.; Prasad, S.; Bhalerao, A.; Cucullo, L. NRF2 and NF-қB interplay in cerebrovascular and neurodegenerative disorders: Molecular mechanisms and possible therapeutic approaches. Redox Biol.,  2019, 21, 101059.
 [http://dx.doi.org/10.1016/j.redox.2018.11.017] [PMID: 30576920]

[172]
Zgheib, N.K.; Sleiman, F.; Nasreddine, L.; Nasrallah, M.; Nakhoul, N.; Isma’eel, H.; Tamim, H. Short telomere length is associated with aging, central obesity, poor sleep and hypertension in Lebanese individuals. Aging Dis.,  2018, 9(1), 77-89.
 [http://dx.doi.org/10.14336/AD.2017.0310] [PMID: 29392083]
Cite As
Mini-Reviews in Medicinal Chemistry

The Effects of Curcumin on Astrocytes in Common Neurodegenerative Conditions

Abstract

Graphical Abstract
