Experimental cell culture models for investigating neurodegenerative diseases

Yıl 2019, Cilt: 11 Sayı: 2, 835 - 851, 23.06.2019

Ahmi Öz

https://doi.org/10.37212/jcnos.683400

Cited By: 4

Öz

Neurological disorders are an important cause of mortality and constitute 11.84% of total deaths globally according to WHO data 2015. It is estimated to increase up to 12.22% in year 2030. Most common NDs can be account for four main groups such as Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS), Huntington’s disease (HD) and Parkinson’s disease (PD). Among these diseases, only AD is the seventh common death cause worldwide and until recently the therapeutic approaches are still lack to decrease of prevalence. Hence, developing new strategies to understand molecular targets or break down to cascade of cellular degenerative process in the neurodegeneration should be investigated by future studies. In cell culture studies, many types of tissues and cells can be cultivated to be a minimized model to normal or pathophysiological status of disorders. There are lots of methodology or technique to compose efficient and respective neurodegenerative disease models in cell lines such as COS-7, HC2S2, HEK-293, HeLa, Neuro-2a, NSC-34, PC-12, and SH-SY5Y. We indicated best medium formula to growth of neuronal cells as well as differentiation chemicals and time/dosages. In the review it was aimed to summarize not only give information about cell lines, methodological procedures and molecular mechanisms of the diseases but also represent future perspective and offers to this field of neuroscience research.

Anahtar Kelimeler

Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, Cellular models

Kaynakça

• Aiken CT, Tobin AJ, Schweitzer ES. 2004. A cell-based screen for drugs to treat Huntington's disease. Neurobiol Dis. 16(3):546-555.
• Alberio T, Bossi AM, Milli A, Parma E, Gariboldi MB, Tosi G, Lopiano L, Fasano M. 2010. Proteomic analysis of dopamine and alpha-synuclein interplay in a cellular model of Parkinson's disease pathogenesis. FEBS J. 277(23):4909-4919.
• Alvarez-de-la-Rosa M, Silva I, Nilsen J, Perez MM, Garcia-Segura LM, Avila J, Naftolin F. 2005. Estradiol prevents neural tau hyperphosphorylation characteristic of Alzheimer's disease. Ann N Y Acad Sci. 1052:210-224.
• Aquilano K, Vigilanza P, Filomeni G, Rotilio G, Ciriolo MR. 2010. Tau dephosphorylation and microfilaments disruption are upstream events of the anti-proliferative effects of DADS in SH-SY5Y cells. J Cell Mol Med. 14(3):564-577. Araya JA, Ramirez AE, Figueroa-Aroca D, Sotes GJ, Perez C, Becerra J, Saez-Orellana F, Guzman L, Aguayo LG, Fuentealba J. 2014. Modulation of neuronal nicotinic receptor by quinolizidine alkaloids causes neuroprotection on a cellular Alzheimer model. J Alzheimers Dis. 42(1):143-155. Asahi M, Hoshimaru M, Hojo M, Matsuura N, Kikuchi H, Hashimoto N. 1998. Induction of the N-methyl-D-aspartate receptor subunit 1 in the immortalized neuronal progenitor cell line HC2S2 during differentiation into neurons. J Neurosci Res. 52(6):699-708. Bahmad H, Hadadeh O, Chamaa F, Cheaito K, Darwish B, Makkawi AK, Abou-Kheir W. 2017. Modeling Human Neurological and Neurodegenerative Diseases: From Induced Pluripotent Stem Cells to Neuronal Differentiation and Its Applications in Neurotrauma. Front Mol Neurosci. 10:50. Bates GP, Dorsey R, Gusella JF, Hayden MR, Kay C, Leavitt BR, Nance M, Ross CA, Scahill RI, Wetzel R et al. 2015. Huntington disease. Nat Rev Dis Primers. 1:15005. Berger F, Gage FH, Vijayaraghavan S. 1998. Nicotinic receptor-induced apoptotic cell death of hippocampal progenitor cells. J Neurosci. 18(17):6871-6881. Blum D, Torch S, Nissou MF, Benabid AL, Verna JM. 2000. Extracellular toxicity of 6-hydroxydopamine on PC12 cells. Neurosci Lett. 283(3):193-196. Bove J, Prou D, Perier C, Przedborski S. 2005. Toxin-induced models of Parkinson's disease. NeuroRx. 2(3):484-494. Buendia I, Egea J, Parada E, Navarro E, Leon R, Rodriguez-Franco MI, Lopez MG. 2015. The melatonin-N,N-dibenzyl(N-methyl)amine hybrid ITH91/IQM157 affords neuroprotection in an in vitro Alzheimer's model via hemo-oxygenase-1 induction. ACS Chem Neurosci. 6(2):288-296. Cacabelos D, Ayala V, Granado-Serrano AB, Jove M, Torres P, Boada J, Cabre R, Ramirez-Nunez O, Gonzalo H, Soler-Cantero A et al. 2016. Interplay between TDP-43 and docosahexaenoic acid-related processes in amyotrophic lateral sclerosis. Neurobiol Dis. 88:148-160. Cashman NR, Durham HD, Blusztajn JK, Oda K, Tabira T, Shaw IT, Dahrouge S, Antel JP. 1992. Neuroblastoma x spinal cord (NSC) hybrid cell lines resemble developing motor neurons. Dev Dyn. 194(3):209-221. Chang JC, Wu SL, Liu KH, Chen YH, Chuang CS, Cheng FC, Su HL, Wei YH, Kuo SJ, Liu CS. 2016. Allogeneic/xenogeneic transplantation of peptide-labeled mitochondria in Parkinson's disease: restoration of mitochondria functions and attenuation of 6-hydroxydopamine-induced neurotoxicity. Transl Res. 170:40-56 e43. Chen N, Ma J, Zhao Y, Wu M, Yang H, Gong W, Chao J, Li X. 2016. Expression of functional recombinant human fibroblast growth factor 8b and its protective effects on MPP(+)-lesioned PC12 cells. Appl Microbiol Biotechnol. 100(2):625-635. Cheng B, Guo Y, Li C, Ji B, Pan Y, Chen J, Bai B. 2014. Edaravone protected PC12 cells against MPP(+)-cytoxicity via inhibiting oxidative stress and up-regulating heme oxygenase-1 expression. J Neurol Sci. 343(1-2):115-119. Choi BS, Kim H, Lee HJ, Sapkota K, Park SE, Kim S, Kim SJ. 2014. Celastrol from 'Thunder God Vine' protects SH-SY5Y cells through the preservation of mitochondrial function and inhibition of p38 MAPK in a rotenone model of Parkinson's disease. Neurochem Res. 39(1):84-96. Choi JS, Park C, Jeong JW. 2010. AMP-activated protein kinase is activated in Parkinson's disease models mediated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Biochem Biophys Res Commun. 391(1):147-151. Chong PA, Forman-Kay JD. 2016. A New Phase in ALS Research. Structure. 24(9):1435-1436. Condello S, Calabro E, Caccamo D, Curro M, Ferlazzo N, Satriano J, Magazu S, Ientile R. 2012. Protective effects of agmatine in rotenone-induced damage of human SH-SY5Y neuroblastoma cells: fourier transform infrared spectroscopy analysis in a model of Parkinson's disease. Amino Acids. 42(2-3):775-781. Cookson MR, Ince PG, Shaw PJ. 1998. Peroxynitrite and hydrogen peroxide induced cell death in the NSC34 neuroblastoma x spinal cord cell line: role of poly (ADP-ribose) polymerase. J Neurochem. 70(2):501-508. Coskuner-Weber O, Uversky VN. 2018. Insights into the Molecular Mechanisms of Alzheimer's and Parkinson's Diseases with Molecular Simulations: Understanding the Roles of Artificial and Pathological Missense Mutations in Intrinsically Disordered Proteins Related to Pathology. Int J Mol Sci. 19(2). Dadakhujaev S, Noh HS, Jung EJ, Cha JY, Baek SM, Ha JH, Kim DR. 2010. Autophagy protects the rotenone-induced cell death in alpha-synuclein overexpressing SH-SY5Y cells. Neurosci Lett. 472(1):47-52. Das KP, Freudenrich TM, Mundy WR. 2004. Assessment of PC12 cell differentiation and neurite growth: a comparison of morphological and neurochemical measures. Neurotoxicol Teratol. 26(3):397-406. Dauer W, Przedborski S. 2003. Parkinson's disease: mechanisms and models. Neuron. 39(6):889-909. Del Barrio L, Martin-de-Saavedra MD, Romero A, Parada E, Egea J, Avila J, McIntosh JM, Wonnacott S, Lopez MG. 2011. Neurotoxicity induced by okadaic acid in the human neuroblastoma SH-SY5Y line can be differentially prevented by alpha7 and beta2* nicotinic stimulation. Toxicol Sci. 123(1):193-205. Dodurga Y, Gundogdu G, Koc T, Yonguc GN, Kucukatay V, Satiroglu-Tufan NL. 2013. Expression of URG4/URGCP, Cyclin D1, Bcl-2, and Bax genes in retinoic acid treated SH-SY5Y human neuroblastoma cells. Contemp Oncol (Pozn). 17(4):346-349. Dong G, Ferguson JM, Duling AJ, Nicholas RG, Zhang D, Rezvani K, Fang S, Monteiro MJ, Li S, Li XJ et al. 2011. Modeling pathogenesis of Huntington's disease with inducible neuroprogenitor cells. Cell Mol Neurobiol. 31(5):737-747. Duka T, Duka V, Joyce JN, Sidhu A. 2009. Alpha-Synuclein contributes to GSK-3beta-catalyzed Tau phosphorylation in Parkinson's disease models. FASEB J. 23(9):2820-2830. Dupont JL, Janoshazi A, Bellahcene M, Mykita S, de Barry J. 2000. Reversible protein kinase C activation in PC12 cells: effect of NGF treatment. Eur J Neurosci. 12(1):215-226. Eggett CJ, Crosier S, Manning P, Cookson MR, Menzies FM, McNeil CJ, Shaw PJ. 2000. Development and characterisation of a glutamate-sensitive motor neurone cell line. J Neurochem. 74(5):1895-1902. Evangelopoulos ME, Weis J, Kruttgen A. 2005. Signalling pathways leading to neuroblastoma differentiation after serum withdrawal: HDL blocks neuroblastoma differentiation by inhibition of EGFR. Oncogene. 24(20):3309-3318. Fan Y, Li J, Zhang YQ, Jiang LH, Zhang YN, Yan CQ. 2014. Protein kinase C delta mediated cytotoxicity of 6-Hydroxydopamine via sustained extracellular signal-regulated kinase 1/2 activation in PC12 cells. Neurol Res. 36(1):53-64. Fatoba O, Kloster E, Reick C, Saft C, Gold R, Epplen JT, Arning L, Ellrichmann G. 2018. Activation of NPY-Y2 receptors ameliorates disease pathology in the R6/2 mouse and PC12 cell models of Huntington's disease. Exp Neurol. 302:112-128. Feng L, Meng H, Wu F, Cheng B, He X, Wang X, Li Z, Liu S. 2008. Olfactory ensheathing cells conditioned medium prevented apoptosis induced by 6-OHDA in PC12 cells through modulation of intrinsic apoptotic pathways. Int J Dev Neurosci. 26(3-4):323-329. Filograna R, Civiero L, Ferrari V, Codolo G, Greggio E, Bubacco L, Beltramini M, Bisaglia M. 2015. Analysis of the Catecholaminergic Phenotype in Human SH-SY5Y and BE(2)-M17 Neuroblastoma Cell Lines upon Differentiation. PLoS One. 10(8):e0136769. Gallagher HC, Odumeru OA, Regan CM. 2000. Regulation of neural cell adhesion molecule polysialylation state by cell-cell contact and protein kinase C delta. J Neurosci Res. 61(6):636-645. Gehringer MM. 2004. Microcystin-LR and okadaic acid-induced cellular effects: a dualistic response. FEBS Lett. 557(1-3):1-8. Goldstein DS, Sullivan P, Cooney A, Jinsmaa Y, Kopin IJ, Sharabi Y. 2015. Rotenone decreases intracellular aldehyde dehydrogenase activity: implications for the pathogenesis of Parkinson's disease. J Neurochem. 133(1):14-25. Gomez-Santos C, Ferrer I, Reiriz J, Vinals F, Barrachina M, Ambrosio S. 2002. MPP+ increases alpha-synuclein expression and ERK/MAP-kinase phosphorylation in human neuroblastoma SH-SY5Y cells. Brain Res. 935(1-2):32-39. Gong P, Deng F, Zhang W, Ji J, Liu J, Sun Y, Hu J. 2017. Tectorigenin attenuates the MPP(+)-induced SH-SY5Y cell damage, indicating a potential beneficial role in Parkinson's disease by oxidative stress inhibition. Exp Ther Med. 14(5):4431-4437. Gorman AM, Szegezdi E, Quigney DJ, Samali A. 2005. Hsp27 inhibits 6-hydroxydopamine-induced cytochrome c release and apoptosis in PC12 cells. Biochem Biophys Res Commun. 327(3):801-810. Han X, Zhu S, Wang B, Chen L, Li R, Yao W, Qu Z. 2014. Antioxidant action of 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cytotoxicity. Neurochem Int. 64:18-23. Hanspal MA, Dobson CM, Yerbury JJ, Kumita JR. 2017. The relevance of contact-independent cell-to-cell transfer of TDP-43 and SOD1 in amyotrophic lateral sclerosis. Biochim Biophys Acta. 1863(11):2762-2771. Hasegawa M. 2016. Molecular Mechanisms in the Pathogenesis of Alzheimer's disease and Tauopathies-Prion-Like Seeded Aggregation and Phosphorylation. Biomolecules. 6(2). Hegarty SV, O'Leary E, Solger F, Stanicka J, Sullivan AM, O'Keeffe GW. 2016. A Small Molecule Activator of p300/CBP Histone Acetyltransferase Promotes Survival and Neurite Growth in a Cellular Model of Parkinson's Disease. Neurotox Res. 30(3):510-520. Hettiarachchi NT, Parker A, Dallas ML, Pennington K, Hung CC, Pearson HA, Boyle JP, Robinson P, Peers C. 2009. alpha-Synuclein modulation of Ca2+ signaling in human neuroblastoma (SH-SY5Y) cells. J Neurochem. 111(5):1192-1201. Hoshimaru M, Ray J, Sah DW, Gage FH. 1996. Differentiation of the immortalized adult neuronal progenitor cell line HC2S2 into neurons by regulatable suppression of the v-myc oncogene. Proc Natl Acad Sci U S A. 93(4):1518-1523. Hou XO, Si JM, Ren HG, Chen D, Wang HF, Ying Z, Hu QS, Gao F, Wang GH. 2015. Parkin represses 6-hydroxydopamine-induced apoptosis via stabilizing scaffold protein p62 in PC12 cells. Acta Pharmacol Sin. 36(11):1300-1307. Huang JZ, Chen YZ, Su M, Zheng HF, Yang YP, Chen J, Liu CF. 2010. dl-3-n-Butylphthalide prevents oxidative damage and reduces mitochondrial dysfunction in an MPP(+)-induced cellular model of Parkinson's disease. Neurosci Lett. 475(2):89-94. Im AR, Kim YH, Uddin MR, Chae S, Lee HW, Kim YS, Lee MY. 2013. Neuroprotective effects of Lycium chinense Miller against rotenone-induced neurotoxicity in PC12 cells. Am J Chin Med. 41(6):1343-1359. Ito S, Nakaso K, Imamura K, Takeshima T, Nakashima K. 2010. Endogenous catecholamine enhances the dysfunction of unfolded protein response and alpha-synuclein oligomerization in PC12 cells overexpressing human alpha-synuclein. Neurosci Res. 66(1):124-130. Jagmag SA, Tripathi N, Shukla SD, Maiti S, Khurana S. 2015. Evaluation of Models of Parkinson's Disease. Front Neurosci. 9:503. Jalava A, Akerman K, Heikkila J. 1993. Protein kinase inhibitor, staurosporine, induces a mature neuronal phenotype in SH-SY5Y human neuroblastoma cells through an alpha-, beta-, and zeta-protein kinase C-independent pathway. J Cell Physiol. 155(2):301-312. Jalava A, Heikkila J, Lintunen M, Akerman K, Pahlman S. 1992. Staurosporine induces a neuronal phenotype in SH-SY5Y human neuroblastoma cells that resembles that induced by the phorbol ester 12-O-tetradecanoyl phorbol-13 acetate (TPA). FEBS Lett. 300(2):114-118. Jamsa A, Hasslund K, Cowburn RF, Backstrom A, Vasange M. 2004. The retinoic acid and brain-derived neurotrophic factor differentiated SH-SY5Y cell line as a model for Alzheimer's disease-like tau phosphorylation. Biochem Biophys Res Commun. 319(3):993-1000. Jiang BP, Le L, Xu LJ, Xiao PG. 2014. Minocycline inhibits ICAD degradation and the NF-kappaB activation induced by 6-OHDA in PC12 cells. Brain Res. 1586:1-11. Jiang M, Yun Q, Shi F, Niu G, Gao Y, Xie S, Yu S. 2016. Downregulation of miR-384-5p attenuates rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through inhibiting endoplasmic reticulum stress. Am J Physiol Cell Physiol. 310(9):C755-763. Jing X, Shi H, Zhang C, Ren M, Han M, Wei X, Zhang X, Lou H. 2015. Dimethyl fumarate attenuates 6-OHDA-induced neurotoxicity in SH-SY5Y cells and in animal model of Parkinson's disease by enhancing Nrf2 activity. Neuroscience. 286:131-140. Jing X, Wei X, Ren M, Wang L, Zhang X, Lou H. 2016. Neuroprotective Effects of Tanshinone I Against 6-OHDA-Induced Oxidative Stress in Cellular and Mouse Model of Parkinson's Disease Through Upregulating Nrf2. Neurochem Res. 41(4):779-786. Jodeiri Farshbaf M, Forouzanfar M, Ghaedi K, Kiani-Esfahani A, Peymani M, Shoaraye Nejati A, Izadi T, Karbalaie K, Noorbakhshnia M, Rahgozar S et al. 2016. Nurr1 and PPARgamma protect PC12 cells against MPP(+) toxicity: involvement of selective genes, anti-inflammatory, ROS generation, and antimitochondrial impairment. Mol Cell Biochem. 420(1-2):29-42. Kang SY, Lee SB, Kim HJ, Kim HT, Yang HO, Jang W. 2017. Autophagic modulation by rosuvastatin prevents rotenone-induced neurotoxicity in an in vitro model of Parkinson's disease. Neurosci Lett. 642:20-26. Kanjilal B, Keyser BM, Andres DK, Nealley E, Benton B, Melber AA, Andres JF, Letukas VA, Clark O, Ray R. 2014. Differentiated NSC-34 cells as an in vitro cell model for VX. Toxicol Mech Methods. 24(7):488-494. Khwanraj K, Madlah S, Grataitong K, Dharmasaroja P. 2016. Comparative mRNA Expression of eEF1A Isoforms and a PI3K/Akt/mTOR Pathway in a Cellular Model of Parkinson's Disease. Parkinsons Dis. 2016:8716016. Kim IS, Ko HM, Koppula S, Kim BW, Choi DK. 2011. Protective effect of Chrysanthemum indicum Linne against 1-methyl-4-phenylpridinium ion and lipopolysaccharide-induced cytotoxicity in cellular model of Parkinson's disease. Food Chem Toxicol. 49(4):963-973. Kim S, Park SE, Sapkota K, Kim MK, Kim SJ. 2011. Leaf extract of Rhus verniciflua Stokes protects dopaminergic neuronal cells in a rotenone model of Parkinson's disease. J Pharm Pharmacol. 63(10):1358-1367. Koistinen NA, Bacanu S, Iverfeldt K. 2016. Phosphorylation of Fe65 amyloid precursor protein-binding protein in response to neuronal differentiation. Neurosci Lett. 613:54-59. Korecka JA, van Kesteren RE, Blaas E, Spitzer SO, Kamstra JH, Smit AB, Swaab DF, Verhaagen J, Bossers K. 2013. Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 8(5):e63862. Kukkonen JP, Shariatmadari R, Courtney MJ, Akerman KE. 1997. Localization of voltage-sensitive Ca2+ fluxes and neuropeptide Y immunoreactivity to varicosities in SH-SY5Y human neuroblastoma cells differentiated by treatment with the protein kinase inhibitor staurosporine. Eur J Neurosci. 9(1):140-150. Kumaran A, Ho CC, Hwang LS. 2018. Protective effect of Nelumbo nucifera extracts on beta amyloid protein induced apoptosis in PC12 cells, in vitro model of Alzheimer's disease. J Food Drug Anal. 26(1):172-181. Kunzler A, Kolling EA, da Silva JD, Jr., Gasparotto J, de Bittencourt Pasquali MA, Moreira JCF, Gelain DP. 2017. Retinol (Vitamin A) Increases alpha-Synuclein, beta-Amyloid Peptide, Tau Phosphorylation and RAGE Content in Human SH-SY5Y Neuronal Cell Line. Neurochem Res. 42(10):2788-2797. La Cognata V, Maugeri G, D'Amico AG, Saccone S, Federico C, Cavallaro S, D'Agata V. 2018. Differential expression of PARK2 splice isoforms in an in vitro model of dopaminergic-like neurons exposed to toxic insults mimicking Parkinson's disease. J Cell Biochem. 119(1):1062-1073. Labbadia J, Morimoto RI. 2013. Huntington's disease: underlying molecular mechanisms and emerging concepts. Trends Biochem Sci. 38(8):378-385. Lamine A, Letourneau M, Doan ND, Maucotel J, Couvineau A, Vaudry H, Chatenet D, Vaudry D, Fournier A. 2016. Characterizations of a synthetic pituitary adenylate cyclase-activating polypeptide analog displaying potent neuroprotective activity and reduced in vivo cardiovascular side effects in a Parkinson's disease model. Neuropharmacology. 108:440-450. Lazaro DF, Pavlou MAS, Outeiro TF. 2017. Cellular models as tools for the study of the role of alpha-synuclein in Parkinson's disease. Exp Neurol. 298(Pt B):162-171. Lee ES, Jeong SJ, Kim YH, Jeon CJ. 2015. Transplantation of Neuro2a Cells into the Developing Postnatal Mouse Eye. Acta Histochem Cytochem. 48(6):205-214. Lee KW, Im JY, Woo JM, Grosso H, Kim YS, Cristovao AC, Sonsalla PK, Schuster DS, Jalbut MM, Fernandez JR et al. 2013. Neuroprotective and anti-inflammatory properties of a coffee component in the MPTP model of Parkinson's disease. Neurotherapeutics. 10(1):143-153. Leuba G, Walzer C, Vernay A, Carnal B, Kraftsik R, Piotton F, Marin P, Bouras C, Savioz A. 2008. Postsynaptic density protein PSD-95 expression in Alzheimer's disease and okadaic acid induced neuritic retraction. Neurobiol Dis. 30(3):408-419. Li GZ, Liu F, Xu C, Li JY, Xu YJ. 2017. Selenium and Zinc against Abeta25-35-Induced Cytotoxicity and Tau Phosphorylation in PC12 Cells and Inhibits gamma-cleavage of APP. Biol Trace Elem Res. Li H, Cao L, Ren Y, Jiang Y, Xie W, Li D. 2017. GLP-1 receptor regulates cell growth through regulating IDE expression level in Abeta1-42-treated PC12 cells. Biosci Rep. Li W, Jiang M, Xiao Y, Zhang X, Cui S, Huang G. 2015. Folic acid inhibits tau phosphorylation through regulation of PP2A methylation in SH-SY5Y cells. J Nutr Health Aging. 19(2):123-129. Li X, Chen W, Zhang L, Liu WB, Fei Z. 2013. Inhibition of store-operated calcium entry attenuates MPP(+)-induced oxidative stress via preservation of mitochondrial function in PC12 cells: involvement of Homer1a. PLoS One. 8(12):e83638. Lin CM, Lin YT, Lin RD, Huang WJ, Lee MH. 2015. Neurocytoprotective Effects of Aliphatic Hydroxamates from Lovastatin, a Secondary Metabolite from Monascus-Fermented Red Mold Rice, in 6-Hydroxydopamine (6-OHDA)-Treated Nerve Growth Factor (NGF)-Differentiated PC12 Cells. ACS Chem Neurosci. 6(5):716-724. Liscic RM, Breljak D. 2011. Molecular basis of amyotrophic lateral sclerosis. Prog Neuropsychopharmacol Biol Psychiatry. 35(2):370-372. Liu H, Mao P, Wang J, Wang T, Xie CH. 2015. Allicin Protects PC12 Cells Against 6-OHDA-Induced Oxidative Stress and Mitochondrial Dysfunction via Regulating Mitochondrial Dynamics. Cell Physiol Biochem. 36(3):966-979. Liu H, Yu C, Xu T, Zhang X, Dong M. 2016. Synergistic protective effect of paeoniflorin and beta-ecdysterone against rotenone-induced neurotoxicity in PC12 cells. Apoptosis. 21(12):1354-1365. Liu Y, Hettinger CL, Zhang D, Rezvani K, Wang X, Wang H. 2014. Sulforaphane enhances proteasomal and autophagic activities in mice and is a potential therapeutic reagent for Huntington's disease. J Neurochem. 129(3):539-547. Lopes FM, da Motta LL, De Bastiani MA, Pfaffenseller B, Aguiar BW, de Souza LF, Zanatta G, Vargas DM, Schonhofen P, Londero GF et al. 2017. RA Differentiation Enhances Dopaminergic Features, Changes Redox Parameters, and Increases Dopamine Transporter Dependency in 6-Hydroxydopamine-Induced Neurotoxicity in SH-SY5Y Cells. Neurotox Res. 31(4):545-559. Lu JYD, Su P, Barber JEM, Nash JE, Le AD, Liu F, Wong AHC. 2017. The neuroprotective effect of nicotine in Parkinson's disease models is associated with inhibiting PARP-1 and caspase-3 cleavage. PeerJ. 5:e3933. Lu M, Su C, Qiao C, Bian Y, Ding J, Hu G. 2016. Metformin Prevents Dopaminergic Neuron Death in MPTP/P-Induced Mouse Model of Parkinson's Disease via Autophagy and Mitochondrial ROS Clearance. Int J Neuropsychopharmacol. 19(9). Madji Hounoum B, Vourc'h P, Felix R, Corcia P, Patin F, Gueguinou M, Potier-Cartereau M, Vandier C, Raoul C, Andres CR et al. 2016. NSC-34 Motor Neuron-Like Cells Are Unsuitable as Experimental Model for Glutamate-Mediated Excitotoxicity. Front Cell Neurosci. 10:118. Martin-Clemente B, Alvarez-Castelao B, Mayo I, Sierra AB, Diaz V, Milan M, Farinas I, Gomez-Isla T, Ferrer I, Castano JG. 2004. alpha-Synuclein expression levels do not significantly affect proteasome function and expression in mice and stably transfected PC12 cell lines. J Biol Chem. 279(51):52984-52990. Mei J, Niu C. 2015. Protective and reversal effects of conserved dopamine neurotrophic factor on PC12 cells following 6-hydroxydopamine administration. Mol Med Rep. 12(1):297-302. Meng H, Li C, Feng L, Cheng B, Wu F, Wang X, Li Z, Liu S. 2007. Effects of Ginkgolide B on 6-OHDA-induced apoptosis and calcium over load in cultured PC12. Int J Dev Neurosci. 25(8):509-514. Mollereau C, Zajac JM, Roumy M. 2007. Staurosporine differentiation of NPFF2 receptor-transfected SH-SY5Y neuroblastoma cells induces selectivity of NPFF activity towards opioid receptors. Peptides. 28(5):1125-1128. Montilla-Lopez P, Munoz-Agueda MC, Feijoo Lopez M, Munoz-Castaneda JR, Bujalance-Arenas I, Tunez-Finana I. 2002. Comparison of melatonin versus vitamin C on oxidative stress and antioxidant enzyme activity in Alzheimer's disease induced by okadaic acid in neuroblastoma cells. Eur J Pharmacol. 451(3):237-243. Moujalled D, Grubman A, Acevedo K, Yang S, Ke YD, Moujalled DM, Duncan C, Caragounis A, Perera ND, Turner BJ et al. 2017. TDP-43 mutations causing amyotrophic lateral sclerosis are associated with altered expression of RNA-binding protein hnRNP K and affect the Nrf2 antioxidant pathway. Hum Mol Genet. 26(9):1732-1746. Mu X, He G, Cheng Y, Li X, Xu B, Du G. 2009. Baicalein exerts neuroprotective effects in 6-hydroxydopamine-induced experimental parkinsonism in vivo and in vitro. Pharmacol Biochem Behav. 92(4):642-648. Munch C, O'Brien J, Bertolotti A. 2011. Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells. Proc Natl Acad Sci U S A. 108(9):3548-3553. Narain Y, Wyttenbach A, Rankin J, Furlong RA, Rubinsztein DC. 1999. A molecular investigation of true dominance in Huntington's disease. J Med Genet. 36(10):739-746. Naziroglu M, Muhamad S, Pecze L. 2017. Nanoparticles as potential clinical therapeutic agents in Alzheimer's disease: focus on selenium nanoparticles. Expert Rev Clin Pharmacol. 10(7):773-782. Ohtsuka T, Asahi M, Matsuura N, Kikuchi H, Hojo M, Kageyama R, Ohkubo H, Hoshimaru M. 1998. Regulated expression of neurogenic basic helix-loop-helix transcription factors during differentiation of the immortalized neuronal progenitor cell line HC2S2 into neurons. Cell Tissue Res. 293(1):23-29. Olatunji OJ, Feng Y, Olatunji OO, Tang J, Ouyang Z, Su Z. 2016. Cordycepin protects PC12 cells against 6-hydroxydopamine induced neurotoxicity via its antioxidant properties. Biomed Pharmacother. 81:7-14. Ostrovskaya RU, Vakhitova YV, Kuzmina U, Salimgareeva M, Zainullina LF, Gudasheva TA, Vakhitov VA, Seredenin SB. 2014. Neuroprotective effect of novel cognitive enhancer noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation. J Biomed Sci. 21:74. Oz A, Celik O. 2016. Curcumin inhibits oxidative stress-induced TRPM2 channel activation, calcium ion entry and apoptosis values in SH-SY5Y neuroblastoma cells: Involvement of transfection procedure. Mol Membr Biol. 33(3-5):76-88. Park EM, Cho BP, Volpe BT, Cruz MO, Joh TH, Cho S. 2005. Ibuprofen protects ischemia-induced neuronal injury via up-regulating interleukin-1 receptor antagonist expression. Neuroscience. 132(3):625-631. Park HJ, Park KH, Shin KS, Lee MK. 2013. The roles of cyclic AMP-ERK-Bad signaling pathways on 6-hydroxydopamine-induced cell survival and death in PC12 cells. Toxicol In Vitro. 27(8):2233-2241. Perier C, Bove J, Vila M, Przedborski S. 2003. The rotenone model of Parkinson's disease. Trends Neurosci. 26(7):345-346. Przedborski S, Vila M, Jackson-Lewis V. 2003. Neurodegeneration: what is it and where are we? J Clin Invest. 111(1):3-10. Pyszko JA, Strosznajder JB. 2014. The key role of sphingosine kinases in the molecular mechanism of neuronal cell survival and death in an experimental model of Parkinson's disease. Folia Neuropathol. 52(3):260-269. Qian JJ, Cheng YB, Yang YP, Mao CJ, Qin ZH, Li K, Liu CF. 2008. Differential effects of overexpression of wild-type and mutant human alpha-synuclein on MPP+-induced neurotoxicity in PC12 cells. Neurosci Lett. 435(2):142-146. Qin J, Wu M, Yu S, Gao X, Zhang J, Dong X, Ji J, Zhang Y, Zhou L, Zhang Q et al. 2015. Pyrroloquinoline quinone-conferred neuroprotection in rotenone models of Parkinson's disease. Toxicol Lett. 238(3):70-82. Rajendra Kopalli S, Koppula S, Shin KY, Noh SJ, Jin Q, Hwang BY, Suh YH. 2012. SF-6 attenuates 6-hydroxydopamine-induced neurotoxicity: an in vitro and in vivo investigation in experimental models of Parkinson's disease. J Ethnopharmacol. 143(2):686-694. Ramalingam M, Kim SJ. 2016. Insulin on activation of autophagy with integrins and syndecans against MPP(+)-induced alpha-synuclein neurotoxicity. Neurosci Lett. 633:94-100. Romero A, Egea J, Gonzalez-Munoz GC, Martin de Saavedra MD, del Barrio L, Rodriguez-Franco MI, Conde S, Lopez MG, Villarroya M, de los Rios C. 2014. ITH12410/SC058: a new neuroprotective compound with potential in the treatment of Alzheimer's disease. ACS Chem Neurosci. 5(9):770-775. Ryu HW, Oh WK, Jang IS, Park J. 2013. Amurensin G induces autophagy and attenuates cellular toxicities in a rotenone model of Parkinson's disease. Biochem Biophys Res Commun. 433(1):121-126. Santos NA, Martins NM, Sisti FM, Fernandes LS, Ferreira RS, Queiroz RH, Santos AC. 2015. The neuroprotection of cannabidiol against MPP(+)-induced toxicity in PC12 cells involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and might be relevant to Parkinson's disease. Toxicol In Vitro. 30(1 Pt B):231-240. Schapira AH. 2008. Mitochondria in the aetiology and pathogenesis of Parkinson's disease. The Lancet Neurology. 7(1):97-109. Sever M, Turkyilmaz M, Sevinc C, Cakir A, Ocalan B, Cansev M, Guler MO, Tekinay AB. 2016. Regenerative effects of peptide nanofibers in an experimental model of Parkinson's disease. Acta Biomater. 46:79-90. Sharma M, Sharma P, Pant HC. 1999. CDK-5-mediated neurofilament phosphorylation in SHSY5Y human neuroblastoma cells. J Neurochem. 73(1):79-86. Shindo Y, Yamanaka R, Suzuki K, Hotta K, Oka K. 2015. Intracellular magnesium level determines cell viability in the MPP(+) model of Parkinson's disease. Biochim Biophys Acta. 1853(12):3182-3191. Simola N, Morelli M, Carta AR. 2007. The 6-hydroxydopamine model of Parkinson's disease. Neurotox Res. 11(3-4):151-167. Smith WW, Margolis RL, Li X, Troncoso JC, Lee MK, Dawson VL, Dawson TM, Iwatsubo T, Ross CA. 2005. Alpha-synuclein phosphorylation enhances eosinophilic cytoplasmic inclusion formation in SH-SY5Y cells. J Neurosci. 25(23):5544-5552. Solesio ME, Saez-Atienzar S, Jordan J, Galindo MF. 2012. Characterization of mitophagy in the 6-hydoxydopamine Parkinson's disease model. Toxicol Sci. 129(2):411-420. Soto C. 2003. Unfolding the role of protein misfolding in neurodegenerative diseases. Nat Rev Neurosci. 4(1):49-60. Sun H, He X, Liu C, Li L, Zhou R, Jin T, Yue S, Feng D, Gong J, Sun J et al. 2017. Effect of Oleracein E, a Neuroprotective Tetrahydroisoquinoline, on Rotenone-Induced Parkinson's Disease Cell and Animal Models. ACS Chem Neurosci. 8(1):155-164. Sun HJ, Wang Y, Hao T, Wang CY, Wang QY, Jiang XX. 2016. Efficient GSH delivery using PAMAM-GSH into MPP-induced PC12 cellular model for Parkinson's disease. Regen Biomater. 3(5):299-307. Talbott EO, Malek AM, Lacomis D. 2016. The epidemiology of amyotrophic lateral sclerosis. Handb Clin Neurol. 138:225-238. Tettamanti G, Prinetti A, Bassi R, Viani P, Giussani P, Riboni L. 1996. Sphingoid bioregulators in the differentiation of cells of neural origin. J Lipid Mediat Cell Signal. 14(1-3):263-275. Tieu K, Zuo DM, Yu PH. 1999. Differential effects of staurosporine and retinoic acid on the vulnerability of the SH-SY5Y neuroblastoma cells: involvement of bcl-2 and p53 proteins. J Neurosci Res. 58(3):426-435. Tofaris GK, Layfield R, Spillantini MG. 2001. alpha-synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome. FEBS Lett. 509(1):22-26. Tovar YRLB, Santa-Cruz LD, Tapia R. 2009. Experimental models for the study of neurodegeneration in amyotrophic lateral sclerosis. Mol Neurodegener. 4:31. Tremblay RG, Sikorska M, Sandhu JK, Lanthier P, Ribecco-Lutkiewicz M, Bani-Yaghoub M. 2010. Differentiation of mouse Neuro 2A cells into dopamine neurons. J Neurosci Methods. 186(1):60-67. Tysnes OB, Storstein A. 2017. Epidemiology of Parkinson's disease. J Neural Transm (Vienna). 124(8):901-905. Uberti D, Rizzini C, Spano PF, Memo M. 1997. Characterization of tau proteins in human neuroblastoma SH-SY5Y cell line. Neurosci Lett. 235(3):149-153. Um M, Gross AW, Lodish HF. 2007. A "classical" homodimeric erythropoietin receptor is essential for the antiapoptotic effects of erythropoietin on differentiated neuroblastoma SH-SY5Y and pheochromocytoma PC-12 cells. Cell Signal. 19(3):634-645. van Hagen M, Piebes DGE, de Leeuw WC, Vuist IM, van Roon-Mom WMC, Moerland PD, Verschure PJ. 2017. The dynamics of early-state transcriptional changes and aggregate formation in a Huntington's disease cell model. BMC Genomics. 18(1):373. Van Laar VS, Berman SB, Hastings TG. 2016. Mic60/mitofilin overexpression alters mitochondrial dynamics and attenuates vulnerability of dopaminergic cells to dopamine and rotenone. Neurobiol Dis. 91:247-261. Verhaar R, Drukarch B, Bol JG, Jongenelen CA, Musters RJ, Wilhelmus MM. 2012. Increase in endoplasmic reticulum-associated tissue transglutaminase and enzymatic activation in a cellular model of Parkinson's disease. Neurobiol Dis. 45(3):839-850. Verhaar R, Jongenelen CA, Gerard M, Baekelandt V, Van Dam AM, Wilhelmus MM, Drukarch B. 2011. Blockade of enzyme activity inhibits tissue transglutaminase-mediated transamidation of alpha-synuclein in a cellular model of Parkinson's disease. Neurochem Int. 58(7):785-793. Vidoni C, Castiglioni A, Seca C, Secomandi E, Melone MA, Isidoro C. 2016. Dopamine exacerbates mutant Huntingtin toxicity via oxidative-mediated inhibition of autophagy in SH-SY5Y neuroblastoma cells: Beneficial effects of anti-oxidant therapeutics. Neurochem Int. 101:132-143. Vidoni C, Secomandi E, Castiglioni A, Melone MAB, Isidoro C. 2017. Resveratrol protects neuronal-like cells expressing mutant Huntingtin from dopamine toxicity by rescuing ATG4-mediated autophagosome formation. Neurochem Int. Wada T, Goparaju SK, Tooi N, Inoue H, Takahashi R, Nakatsuji N, Aiba K. 2012. Amyotrophic lateral sclerosis model derived from human embryonic stem cells overexpressing mutant superoxide dismutase 1. Stem Cells Transl Med. 1(5):396-402. Wang F, Jia Y, Liu J, Zhai J, Cao N, Yue W, He H, Pei X. 2017. Dental pulp stem cells promote regeneration of damaged neuron cells on the cellular model of Alzheimer's disease. Cell Biol Int. 41(6):639-650. Wang GH, Mitsui K, Kotliarova S, Yamashita A, Nagao Y, Tokuhiro S, Iwatsubo T, Kanazawa I, Nukina N. 1999. Caspase activation during apoptotic cell death induced by expanded polyglutamine in N2a cells. Neuroreport. 10(12):2435-2438. Wang H, Jiang T, Li W, Gao N, Zhang T. 2018. Resveratrol attenuates oxidative damage through activating mitophagy in an in vitro model of Alzheimer's disease. Toxicol Lett. 282:100-108. Wang H, Lim PJ, Yin C, Rieckher M, Vogel BE, Monteiro MJ. 2006. Suppression of polyglutamine-induced toxicity in cell and animal models of Huntington's disease by ubiquilin. Hum Mol Genet. 15(6):1025-1041. Wang S, Zhang X, Guo Y, Rong H, Liu T. 2017. The long noncoding RNA HOTAIR promotes Parkinson's disease by upregulating LRRK2 expression. Oncotarget. 8(15):24449-24456. Wang YP, Li XT, Liu SJ, Zhou XW, Wang XC, Wang JZ. 2004. Melatonin ameliorated okadaic-acid induced Alzheimer-like lesions. Acta Pharmacol Sin. 25(3):276-280. Westergard T, Jensen BK, Wen X, Cai J, Kropf E, Iacovitti L, Pasinelli P, Trotti D. 2016. Cell-to-Cell Transmission of Dipeptide Repeat Proteins Linked to C9orf72-ALS/FTD. Cell Rep. 17(3):645-652. Williams AJ, Paulson HL. 2008. Polyglutamine neurodegeneration: protein misfolding revisited. Trends Neurosci. 31(10):521-528. Wong HK, Bauer PO, Kurosawa M, Goswami A, Washizu C, Machida Y, Tosaki A, Yamada M, Knopfel T, Nakamura T et al. 2008. Blocking acid-sensing ion channel 1 alleviates Huntington's disease pathology via an ubiquitin-proteasome system-dependent mechanism. Hum Mol Genet. 17(20):3223-3235. worldwide Ttcod. Wu F, Wang Z, Gu JH, Ge JB, Liang ZQ, Qin ZH. 2013. p38(MAPK)/p53-Mediated Bax induction contributes to neurons degeneration in rotenone-induced cellular and rat models of Parkinson's disease. Neurochem Int. 63(3):133-140. Wu F, Xu HD, Guan JJ, Hou YS, Gu JH, Zhen XC, Qin ZH. 2015. Rotenone impairs autophagic flux and lysosomal functions in Parkinson's disease. Neuroscience. 284:900-911. Wyttenbach A, Swartz J, Kita H, Thykjaer T, Carmichael J, Bradley J, Brown R, Maxwell M, Schapira A, Orntoft TF et al. 2001. Polyglutamine expansions cause decreased CRE-mediated transcription and early gene expression changes prior to cell death in an inducible cell model of Huntington's disease. Hum Mol Genet. 10(17):1829-1845. Xie H, Hu H, Chang M, Huang D, Gu X, Xiong X, Xiong R, Hu L, Li G. 2016. Identification of chaperones in a MPP(+)-induced and ATRA/TPA-differentiated SH-SY5Y cell PD model. Am J Transl Res. 8(12):5659-5671. Xie HR, Hu LS, Li GY. 2010. SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson's disease. Chin Med J (Engl). 123(8):1086-1092. Yan JQ, Sun JC, Zhai MM, Cheng LN, Bai XL, Feng CL. 2015. Lovastatin induces neuroprotection by inhibiting inflammatory cytokines in 6-hydroxydopamine treated microglia cells. Int J Clin Exp Med. 8(6):9030-9037. Yan W, Chen ZY, Chen JQ, Chen HM. 2018. LncRNA NEAT1 promotes autophagy in MPTP-induced Parkinson's disease through stabilizing PINK1 protein. Biochem Biophys Res Commun. 496(4):1019-1024. Yan X, Chen T, Zhang L, Du H. 2017. Protective effects of Forsythoside A on amyloid beta-induced apoptosis in PC12 cells by downregulating acetylcholinesterase. Eur J Pharmacol. 810:141-148. Yang CP, Zhang ZH, Zhang LH, Rui HC. 2016. Neuroprotective Role of MicroRNA-22 in a 6-Hydroxydopamine-Induced Cell Model of Parkinson's Disease via Regulation of Its Target Gene TRPM7. J Mol Neurosci. 60(4):445-452. Yang YX, Wood NW, Latchman DS. 2009. Molecular basis of Parkinson's disease. Neuroreport. 20(2):150-156. Ye Q, Zhang X, Huang B, Zhu Y, Chen X. 2013. Astaxanthin suppresses MPP(+)-induced oxidative damage in PC12 cells through a Sp1/NR1 signaling pathway. Mar Drugs. 11(4):1019-1034. Yong-Kee CJ, Sidorova E, Hanif A, Perera G, Nash JE. 2012. Mitochondrial dysfunction precedes other sub-cellular abnormalities in an in vitro model linked with cell death in Parkinson's disease. Neurotox Res. 21(2):185-194. Yuan YH, Yan WF, Sun JD, Huang JY, Mu Z, Chen NH. 2015. The molecular mechanism of rotenone-induced alpha-synuclein aggregation: emphasizing the role of the calcium/GSK3beta pathway. Toxicol Lett. 233(2):163-171. Yuan Z, Luan G, Wang Z, Hao X, Li J, Suo Y, Li G, Wang H. 2017. Flavonoids from Potentilla parvifolia Fisch. and Their Neuroprotective Effects in Human Neuroblastoma SH-SY5Y Cells in vitro. Chem Biodivers. 14(6). Yurekli VA, Gurler S, Naziroglu M, Uguz AC, Koyuncuoglu HR. 2013. Zonisamide attenuates MPP+-induced oxidative toxicity through modulation of Ca2+ signaling and caspase-3 activity in neuronal PC12 cells. Cell Mol Neurobiol. 33(2):205-212. Yuste VJ, Sanchez-Lopez I, Sole C, Encinas M, Bayascas JR, Boix J, Comella JX. 2002. The prevention of the staurosporine-induced apoptosis by Bcl-X(L), but not by Bcl-2 or caspase inhibitors, allows the extensive differentiation of human neuroblastoma cells. J Neurochem. 80(1):126-139. Zhang D, Zhang JJ, Liu GT. 2007. The novel squamosamide derivative (compound FLZ) attenuated 1-methyl, 4-phenyl-pyridinium ion (MPP+)-induced apoptosis and alternations of related signal transduction in SH-SY5Y cells. Neuropharmacology. 52(2):423-429. Zhang GF, Zhang Y, Zhao G. 2015. Crocin protects PC12 cells against MPP(+)-induced injury through inhibition of mitochondrial dysfunction and ER stress. Neurochem Int. 89:101-110. Zhang JY, Deng YN, Zhang M, Su H, Qu QM. 2016. SIRT3 Acts as a Neuroprotective Agent in Rotenone-Induced Parkinson Cell Model. Neurochem Res. 41(7):1761-1773. Zhang S, Zhang M, Cai F, Song W. 2013. Biological function of Presenilin and its role in AD pathogenesis. Transl Neurodegener. 2(1):15. Zhang X, Xiong J, Liu S, Wang L, Huang J, Liu L, Yang J, Zhang G, Guo K, Zhang Z et al. 2014. Puerarin protects dopaminergic neurons in Parkinson's disease models. Neuroscience. 280:88-98. Zhao DL, Zou LB, Zhou LF, Zhu P, Zhu HB. 2007. A cell-based model of alpha-synucleinopathy for screening compounds with therapeutic potential of Parkinson's disease. Acta Pharmacol Sin. 28(5):616-626. Zheng M, Liu C, Fan Y, Shi D, Zhang Y. 2016. Protective Effects of Paeoniflorin Against MPP(+)-induced Neurotoxicity in PC12 Cells. Neurochem Res. 41(6):1323-1334. Zhou ZD, Kerk SY, Xiong GG, Lim TM. 2009. Dopamine auto-oxidation aggravates non-apoptotic cell death induced by over-expression of human A53T mutant alpha-synuclein in dopaminergic PC12 cells. J Neurochem. 108(3):601-610. Zou XD, Guo SQ, Hu ZW, Li WL. 2016. NAMPT protects against 6-hydroxydopamine-induced neurotoxicity in PC12 cells through modulating SIRT1 activity. Mol Med Rep. 13(5):4058-4064. Zou Y, Wang R, Guo H, Dong M. 2015. Phytoestrogen beta-Ecdysterone Protects PC12 Cells Against MPP+-Induced Neurotoxicity In Vitro: Involvement of PI3K-Nrf2-Regulated Pathway. Toxicol Sci. 147(1):28-38.