Top

Published in:

Open Access 01-12-2017 | Review

The SH-SY5Y cell line in Parkinson’s disease research: a systematic review

Authors: Helena Xicoy, Bé Wieringa, Gerard J.M. Martens

Published in: Molecular Neurodegeneration | Issue 1/2017

Abstract

Parkinson’s disease (PD) is a devastating and highly prevalent neurodegenerative disease for which only symptomatic treatment is available. In order to develop a truly effective disease-modifying therapy, improvement of our current understanding of the molecular and cellular mechanisms underlying PD pathogenesis and progression is crucial. For this purpose, standardization of research protocols and disease models is necessary. As human dopaminergic neurons, the cells mainly affected in PD, are difficult to obtain and maintain as primary cells, current PD research is mostly performed with permanently established neuronal cell models, in particular the neuroblastoma SH-SY5Y lineage. This cell line is frequently chosen because of its human origin, catecholaminergic (though not strictly dopaminergic) neuronal properties, and ease of maintenance. However, there is no consensus on many fundamental aspects that are associated with its use, such as the effects of culture media composition and of variations in differentiation protocols. Here we present the outcome of a systematic review of scientific articles that have used SH-SY5Y cells to explore PD. We describe the cell source, culture conditions, differentiation protocols, methods/approaches used to mimic PD and the preclinical validation of the SH-SY5Y findings by employing alternative cellular and animal models. Thus, this overview may help to standardize the use of the SH-SY5Y cell line in PD research and serve as a future user’s guide.

Available only for authorised users

Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, Holloway RG, Kieburtz K, et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology. 2007;68(5):384–6.PubMedCrossRef

Wirdefeldt K, Adami H-O, Cole P, Trichopoulos D, Mandel J. Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol. 2011;26 Suppl 1:1–58.CrossRef

Chaudhuri KR, Schapira AH. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol. 2009;8(5):464–74.PubMedCrossRef

Xia R, Mao Z-H. Progression of motor symptoms in Parkinson’s disease. Neurosci Bull. 2012;28(1):39–48.PubMedCrossRef

Dexter DT, Jenner P. Parkinson disease: from pathology to molecular disease mechanisms. Free Radic Biol Med. 2013;62:132–44.PubMedCrossRef

Biedler JL, Roffler-Tarlov S, Schachner M, Freedman LS. Multiple Neurotransmitter Synthesis by Human Neuroblastoma Cell Lines and Clones. Cancer Res. 1978;38(11 Part 1):3751–7.PubMed

Påhlman S, Ruusala A-I, Abrahamsson L, Mattsson MEK, Esscher T. Retinoic acid-induced differentiation of cultured human neuroblastoma cells: a comparison with phorbolester-induced differentiation. Cell Differ. 1984;14(2):135–44.PubMedCrossRef

Ross RA, Biedler JL. Presence and Regulation of Tyrosinase Activity in Human Neuroblastoma Cell Variants in Vitro. Cancer Res. 1985;45(4):1628–32.PubMed

Nagatsu T, Levitt M, Udenfriend S. Tyrosine hydroxylase. The initial step in norepinephrine synthesis. J Biol Chem. 1964;239:2910–7.PubMed

10.

Levin EY, Levenberg B, Kaufman S. The enzymatic conversion of 3,4-dihydroxyphenylethylamine to norepinephrine. J Biol Chem. 1960;235:2080–6.PubMed

11.

Krishna A, Biryukov M, Trefois C, Antony PMA, Hussong R, Lin J, et al. Systems genomics evaluation of the SH-SY5Y neuroblastoma cell line as a model for Parkinson’s disease. BMC Genomics. 2014;15:1154.PubMedPubMedCentralCrossRef

12.

Wu X, Lin M, Li Y, Zhao X, Yan F. Effects of DMEM and RPMI 1640 on the biological behavior of dog periosteum-derived cells. Cytotechnology. 2009;59(2):103–11.PubMedPubMedCentralCrossRef

13.

Huang Z, Shao W, Gu J, Hu X, Shi Y, Xu W, Huang C, Lin D. Effects of culture media on metabolic profiling of the human gastric cancer cell line SGC7901. Mol Biosyst. 2015;11(7):1832–40.PubMedCrossRef

14.

Carey BW, Finley LW, Cross JR, Allis CD, Thompson CB. Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature. 2015;518(7539):413–6.PubMedCrossRef

15.

Mazzio E, Soliman KF. Pyruvic acid cytoprotection against 1-methyl-4-phenylpyridinium, 6-hydroxydopamine and hydrogen peroxide toxicities in vitro. Neurosci Lett. 2003;337(2):77–80.PubMedCrossRef

16.

Wang X, Perez E, Liu R, Yan LJ, Mallet RT, Yang SH. Pyruvate protects mitochondria from oxidative stress in human neuroblastoma SK-N-SH cells. Brain Res. 2007;1132(1):1–9.PubMedCrossRef

17.

van der Valk J, Brunner D, De Smet K, Fex Svenningsen A, Honegger P, Knudsen LE, Lindl T, Noraberg J, Price A, Scarino ML, Gstraunthaler G. Optimization of chemically defined cell culture media--replacing fetal bovine serum in mammalian in vitro methods. Toxicol In Vitro. 2010;24(4):1053–63.PubMedCrossRef

18.

Buttiglione M, Vitiello F, Sardella E, Petrone L, Nardulli M, Favia P, et al. Behaviour of SH-SY5Y neuroblastoma cell line grown in different media and on different chemically modified substrates. Biomaterials. 2007;28(19):2932–45.PubMedCrossRef

19.

Agholme L, Lindström T, Kågedal K, Marcusson J, Hallbeck M. An In Vitro Model for Neuroscience: Differentiation of SH-SY5Y Cells into Cells with Morphological and Biochemical Characteristics of Mature Neurons. J Alzheimer’s Dis. 2010;20(4):1069–82.

20.

Kovalevich J, Langford D. Considerations for the Use of SH-SY5Y Neuroblastoma Cells in Neurobiology. 2013. p. 9–21.

21.

Encinas M, Iglesias M, Liu Y, Wang H, Muhaisen A, Ceña V, et al. Sequential Treatment of SH-SY5Y Cells with Retinoic Acid and Brain-Derived Neurotrophic Factor Gives Rise to Fully Differentiated, Neurotrophic Factor-Dependent, Human Neuron-Like Cells. J Neurochem. 2002;75(3):991–1003.CrossRef

22.

Sarkanen J-R, Nykky J, Siikanen J, Selinummi J, Ylikomi T, Jalonen TO. Cholesterol supports the retinoic acid-induced synaptic vesicle formation in differentiating human SH-SY5Y neuroblastoma cells. J Neurochem. 2007;102(6):1941–52.PubMedCrossRef

23.

Schneider L, Giordano S, Zelickson BR, Johnson SM, Benavides AG, Ouyang X, Fineberg N, Darley-Usmar VM, Zhang J. Differentiation of SH-SY5Y cells to a neuronal phenotype changes cellular bioenergetics and the response to oxidative stress. Free Radic Biol Med. 2011;51(11):2007.PubMedPubMedCentralCrossRef

24.

Teppola H, Sarkanen J-R, Jalonen TO, Linne M-L. Morphological Differentiation Towards Neuronal Phenotype of SH-SY5Y Neuroblastoma Cells by Estradiol, Retinoic Acid and Cholesterol. Neurochem Res. 2016;41(4):731–47.PubMedCrossRef

25.

Yang H, Wang J, Sun J, Liu X, Duan W-M, Qu T. A new method to effectively and rapidly generate neurons from SH-SY5Y cells. Neurosci Lett. 2016;610:43–7.PubMedCrossRef

26.

Lopes FM, Schröder R, da Júnior MLC F, Zanotto-Filho A, Müller CB, Pires AS, et al. Comparison between proliferative and neuron-like SH-SY5Y cells as an in vitro model for Parkinson disease studies. Brain Res. 2010;1337:85–94.PubMedCrossRef

27.

Cheung Y-T, Lau WK-W, Yu M-S, Lai CS-W, Yeung S-C, So K-F, et al. Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research. Neurotoxicology. 2009;30(1):127–35.PubMedCrossRef

28.

Korecka JA, van Kesteren RE, Blaas E, Spitzer SO, Kamstra JH, Smit AB, Swaab DF, Verhaagen J, Bossers K. Phenotypic Characterization of Retinoic Acid Differentiated SH-SY5Y Cells by Transcriptional Profiling. PLoS One. 2013;8(5):e63862.PubMedPubMedCentralCrossRef

29.

Hashemi SH, Li J-Y, Ahlman H, Dahlström A. SSR2(a) receptor expression and adrenergic/cholinergic characteristics in differentiated SH-SY5Y cells. Neurochem Res. 2003;28(3–4):449–60.PubMedCrossRef

30.

Cheng B, Martinez AA, Morado J, Scofield V, Roberts JL, Maffi SK. Retinoic acid protects against proteasome inhibition associated cell death in SH-SY5Y cells via the AKT pathway. Neurochem Int. 2013;62(1):31–42.PubMedCrossRef

31.

Presgraves SP, Borwege S, Millan MJ, Joyce JN. Involvement of dopamine D2/D3 receptors and BDNF in the neuroprotective effects of S32504 and pramipexole against 1-methyl-4-phenylpyridinium in terminally differentiated SH-SY5Y cells. Exp Neurol. 2004;190(1):157–70.PubMedCrossRef

32.

Bellucci A, Collo G, Sarnico I, Battistin L, Missale C, Spano P. Alpha-synuclein aggregation and cell death triggered by energy deprivation and dopamine overload are counteracted by D 2 D 3 receptor activation. J Neurochem. 2008;106(2):560–77.PubMedCrossRef

33.

Knaryan VH, Samantaray S, Park S, Azuma M, Inoue J, Banik NL. SNJ-1945, a calpain inhibitor, protects SH-SY5Y cells against MPP (+) and rotenone. J Neurochem. 2014;130(2):280–90.PubMedCrossRef

34.

Grimm J, Mueller A, Hefti F, Rosenthal A. Molecular basis for catecholaminergic neuron diversity. Proc Natl Acad Sci U S A. 2004;101(38):13891–6.PubMedPubMedCentralCrossRef

35.

Poulin J-F, Zou J, Drouin-Ouellet J, Kim K-YA, Cicchetti F, Awatramani RB. Defining midbrain dopaminergic neuron diversity by single-cell gene expression profiling. Cell Rep. 2014;9(3):930–43.PubMedPubMedCentralCrossRef

36.

Edsjö A, Lavenius E, Nilsson H, Hoehner JC, Simonsson P, Culp LA, Martinsson T, Larsson C, Påhlman S. Expression of trkB in human neuroblastoma in relation to MYCN expression and retinoic acid treatment. Lab Invest. 2003;83(6):813–23.PubMedCrossRef

37.

Goldie BJ, Barnett MM, Cairns MJ. BDNF and the maturation of posttranscriptional regulatory networks in human SH-SY5Y neuroblast differentiation. Front Cell Neurosci. 2014;8:325.PubMedPubMedCentralCrossRef

38.

Mastroeni D, Grover A, Leonard B, Joyce JN, Coleman PD, Kozik B, Bellinger DL, Rogers J. Microglial responses to dopamine in a cell culture model of Parkinson’s disease. Neurobiol Aging. 2009;30(11):1805–17.PubMedCrossRef

39.

Morton AJ, Williams MN, Emson PC, Faull RL. The morphology of human neuroblastoma cell grafts in the kainic acid-lesioned basal ganglia of the rat. J Neurocytol. 1995;24(8):568–84.PubMedCrossRef

40.

Nisar R, Hanson PS, He L, Taylor RW, Blain PG, Morris CM. Diquat causes caspase-independent cell death in SH-SY5Y cells by production of ROS independently of mitochondria. Arch Toxicol. 2015;89(10):1811–25.PubMedPubMedCentralCrossRef

41.

Su C, Yang X, Lou J. Geniposide reduces α-synuclein by blocking microRNA-21/lysosome-associated membrane protein 2A interaction in Parkinson disease models. Brain Res. 2016;1644:98–106.PubMedCrossRef

42.

Hegarty SV, Sullivan AM, O’Keeffe GW. BMP2 and GDF5 induce neuronal differentiation through a Smad dependant pathway in a model of human midbrain dopaminergic neurons. Mol Cell Neurosci. 2013;56:263–71.PubMedCrossRef

43.

Borland MK, Trimmer PA, Rubinstein JD, Keeney PM, Mohanakumar K, Liu L, Bennett Jr JP. Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson’s disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells. Mol Neurodegener. 2008;3:21.PubMedPubMedCentralCrossRef

44.

Ballaz S, Morales I, Rodríguez M, Obeso JA. Ascorbate prevents cell death from prolonged exposure to glutamate in an in vitro model of human dopaminergic neurons. J Neurosci Res. 2013;91(12):1609–17.PubMedCrossRef

45.

Wang T, Chen J, Tang CX, Zhou XY, Gao DS. Inverse Expression Levels of EphrinA3 and EphrinA5 Contribute to Dopaminergic Differentiation of Human SH-SY5Y Cells. J Mol Neurosci. 2016;59(4):483–92.PubMedCrossRef

46.

Xie H, Hu L, Li G. SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson’s disease. Chin Med J (Engl). 2010;123(8):1086–92.

47.

Wu AR, Neff NF, Kalisky T, Dalerba P, Treutlein B, Rothenberg ME, Mburu FM, Mantalas GL, Sim S, Clarke MF, Quake SR. Quantitative assessment of single-cell RNA-sequencing methods. Nat Methods. 2014;11(1):41–6.PubMedCrossRef

48.

Battich N, Stoeger T, Pelkmans L. Control of Transcript Variability in Single Mammalian Cells. Cell. 2015;163(7):1596–610.PubMedCrossRef

49.

Wang H, Imai Y, Kataoka A, Takahashi R. Cell Type-Specific Upregulation of Parkin in Response to ER Stress. Antioxid Redox Signal. 2007;9(5):533–42.PubMedCrossRef

50.

Langston J, Ballard P, Tetrud J, Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983;219(4587):249–54.CrossRef

51.

Vila M, Przedborski S. Neurological diseases: Targeting programmed cell death in neurodegenerative diseases. Nat Rev Neurosci. 2003;4(5):365–75.PubMedCrossRef

52.

Simola N, Morelli M, Carta AR. The 6-hydroxydopamine model of Parkinson’s disease. Neurotox Res. 2007;11(3–4):151–67.PubMedCrossRef

53.

Glinka YY, Youdim MBH. Inhibition of mitochondrial complexes I and IV by 6-hydroxydopamine. Eur J Pharmacol Environ Toxicol Pharmacol. 1995;292(3–4):329–32.CrossRef

54.

Storch A, Kaftan A, Burkhardt K, Schwarz J. 6-Hydroxydopamine toxicity towards human SH-SY5Y dopaminergic neuroblastoma cells: independent of mitochondrial energy metabolism. J Neural Transm. 2000;107(3):0281–93.CrossRef

55.

Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, et al. Rotenone, paraquat, and Parkinson’s disease. Environ Health Perspect. 2011;119(6):866–72.PubMedPubMedCentralCrossRef

56.

Cicchetti F, Drouin-Ouellet J, Gross RE. Environmental toxins and Parkinson’s disease: what have we learned from pesticide-induced animal models? Trends Pharmacol Sci. 2009;30(9):475–83.PubMedCrossRef

57.

Kumaran R, Cookson MR. Pathways to Parkinsonism Redux: convergent pathobiological mechanisms in genetics of Parkinson’s disease. Hum Mol Genet. 2015;24(R1):R32–44.PubMedPubMedCentralCrossRef

58.

Michel PP, Hirsch EC, Hunot S. Understanding Dopaminergic Cell Death Pathways in Parkinson Disease. Neuron. 2016;90(4):675–91.PubMedCrossRef

59.

Exner N, Lutz AK, Haass C, Winklhofer KF. Mitochondrial dysfunction in Parkinson’s disease: molecular mechanisms and pathophysiological consequences. EMBO J. 2012;31(14):3038–62.PubMedPubMedCentralCrossRef

60.

Ryan BJ, Hoek S, Fon EA, Wade-Martins R. Mitochondrial dysfunction and mitophagy in Parkinson’s: from familial to sporadic disease. Trends Biochem Sci. 2015;40(4):200–10.PubMedCrossRef

61.

McNaught KSP, Olanow CW. Protein aggregation in the pathogenesis of familial and sporadic Parkinson’s disease. Neurobiol Aging. 2006;27(4):530–45.PubMedCrossRef

62.

Dehay B, Martinez-Vicente M, Caldwell GA, Caldwell KA, Yue Z, Cookson MR, et al. Lysosomal impairment in Parkinson’s disease. Mov Disord. 2013;28(6):725–32.PubMedPubMedCentralCrossRef

63.

Zhang H, Duan C, Yang H. Defective Autophagy in Parkinson’s Disease: Lessons from Genetics. Mol Neurobiol. 2015;51(1):89–104.PubMedCrossRef

64.

Kahns S, Lykkebo S, Jakobsen LD, Nielsen MS, Jensen PH. Caspase-mediated parkin cleavage in apoptotic cell death. J Biol Chem. 2002;277(18):15303–8.PubMedCrossRef

65.

Muqit MM, Davidson SM, Payne Smith MD, MacCormac LP, Kahns S, Jensen PH, Wood NW, Latchman DS. Parkin is recruited into aggresomes in a stress-specific manner: over-expression of parkin reduces aggresome formation but can be dissociated from parkin’s effect on neuronal survival. Hum Mol Genet. 2004;13(1):117–35.PubMedCrossRef

66.

Petit A, Kawarai T, Paitel E, Sanjo N, Maj M, Scheid M, Chen F, Gu Y, Hasegawa H, Salehi-Rad S, Wang L, Rogaeva E, Fraser P, Robinson B, St George-Hyslop P, Tandon A. Wild-type PINK1 prevents basal and induced neuronal apoptosis, a protective effect abrogated by Parkinson disease-related mutations. J Biol Chem. 2005;280(40):34025–32.PubMedCrossRef

67.

Alves da Costa C, Dunys J, Brau F, Wilk S, Cappai R, Checler F. 6-Hydroxydopamine but not 1-methyl-4-phenylpyridinium abolishes alpha-synuclein anti-apoptotic phenotype by inhibiting its proteasomal degradation and by promoting its aggregation. J Biol Chem. 2006;281(14):9824–31.PubMedCrossRef

68.

Iwashita A, Muramatsu Y, Yamazaki T, Muramoto M, Kita Y, Yamazaki S, Mihara K, Moriguchi A, Matsuoka N. Neuroprotective efficacy of the peroxisome proliferator-activated receptor delta-selective agonists in vitro and in vivo. J Pharmacol Exp Ther. 2007;309(3):1067–78.CrossRef

69.

Ruan Q, Harrington AJ, Caldwell KA, Caldwell GA, Standaert DG. VPS41, a protein involved in lysosomal trafficking, is protective in Caenorhabditis elegans and mammalian cellular models of Parkinson’s disease. Neurobiol Dis. 2010;37(2):330–8.PubMedCrossRef

70.

Jaworska-Feil L, Jantas D, Leskiewicz M, Budziszewska B, Kubera M, Basta-Kaim A, Lipkowski AW, Lason W. Protective effects of TRH and its analogues against various cytotoxic agents in retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells. Neuropeptides. 2010;44(6):495–508.PubMedCrossRef

71.

Kawajiri S, Machida Y, Saiki S, Sato S, Hattori N. Zonisamide reduces cell death in SH-SY5Y cells via an anti-apoptotic effect and by upregulating MnSOD. Neurosci Lett. 2010;481(2):88–91.PubMedCrossRef

72.

Verhaar R, Drukarch B, Bol JG, Jongenelen CA, Musters RJ, Wilhelmus MM. Increase in endoplasmic reticulum-associated tissue transglutaminase and enzymatic activation in a cellular model of Parkinson’s disease. Neurobiol Dis. 2012;58(7):785–93.

73.

Shea TB, Beermann ML. Staurosporine-induced morphological differentiation of human neuroblastoma cells. Cell Biol Int Rep. 1991;15(2):161–8.PubMedCrossRef

74.

Jalava A, Heikkila J, Minnamaija L, Akerman K, Pahlman S. 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. 1992;300(2):114–8.CrossRef

75.

Filograna R, Civiero L, Ferrari V, Codolo G, Greggio E, Bubacco L, et al. Analysis of the Catecholaminergic Phenotype in Human SH-SY5Y and BE (2)-M17 Neuroblastoma Cell Lines upon Differentiation. PLoS ONE. 2015;10(8):e0136769.PubMedPubMedCentralCrossRef

76.

Tofaris GK, Layfield R, Spillantini MG. alpha-synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome. FEBS Lett. 2001;509(1):22–6.PubMedCrossRef

77.

Pandey N, Schmidt RE, Galvin JE. The alpha-synuclein mutation E46K promotes aggregation in cultured cells. Exp Neurol. 2006;197(2):515–20.PubMedCrossRef

78.

Liangliang X, Yonghui H, Shunmei E, Shoufang G, Wei Z, Jiangying Z. Dominant-positive HSF1 decreases alpha-synuclein level and alpha-synuclein-induced toxicity. Mol Biol Rep. 2010;37(4):1875–81.PubMedCrossRef

79.

Hasegawa T, Matsuzaki M, Takeda A, Kikuchi A, Akita H, Perry G, Smith MA, Itoyama Y. Accelerated alpha-synuclein aggregation after differentiation of SH-SY5Y neuroblastoma cells. Brain Res. 2004;1013(1):51–9.PubMedCrossRef

80.

Zhang Z, Cheng Y. miR-16-1 promotes the aberrant α-synuclein accumulation in parkinson disease via targeting heat shock protein 70. ScientificWorldJournal. 2014;2014:938348.PubMedPubMedCentral

81.

Macchi F, Deleersnijder A, Van den Haute C, Munck S, Pottel H, Michiels A, Debyser Z, Gerard M, Baekelandt V. High-content analysis of α-synuclein aggregation and cell death in a cellular model of Parkinson’s disease. J Neurosci Methods. 2016;261:117–27.PubMedCrossRef

82.

Izumi Y, Kondo N, Takahashi R, Akaike A, Kume T. Reduction of Immunoreactivity Against the C-Terminal Region of the Intracellular α-Synuclein by Exogenous α-Synuclein Aggregates: Possibility of Conformational Changes. J Parkinsons Dis. 2016;6(3):569–79.PubMedCrossRef

83.

Xin W, Emadi S, Williams S, Liu Q, Schulz P, He P, Alam NB, Wu J, Sierks MR. Toxic Oligomeric Alpha-Synuclein Variants Present in Human Parkinson’s Disease Brains Are Differentially Generated in Mammalian Cell Models. Biomolecules. 2015;5(3):1634–51.PubMedPubMedCentralCrossRef

84.

Emadi S, Kasturirangan S, Wang MS, Schulz P, Sierks MR. Detecting morphologically distinct oligomeric forms of alpha-synuclein. J Biol Chem. 2009;284(17):11048–58.PubMedPubMedCentralCrossRef

85.

Bennett MC, Bishop JF, Leng Y, Chock PB, Chase TN, Mouradian MM. Degradation of alpha-synuclein by proteasome. J Biol Chem. 1999;274(48):33855–8.PubMedCrossRef

86.

Follett J, Darlow B, Wong MB, Goodwin J, Pountney DL. Potassium depolarization and raised calcium induces α-synuclein aggregates. Neurotox Res. 2013;23(4):378–92.PubMedCrossRef

87.

Gegg ME, Cooper JM, Schapira AH, Taanman JW. Silencing of PINK1 expression affects mitochondrial DNA and oxidative phosphorylation in dopaminergic cells. PLoS One. 2009;4(3):e4756.PubMedPubMedCentralCrossRef

88.

van der Merwe C, van Dyk HC, Engelbrecht L, van der Westhuizen FH, Kinnear C, Loos B6, Bardien S. Curcumin Rescues a PINK1 Knock Down SH-SY5Y Cellular Model of Parkinson’s Disease from Mitochondrial Dysfunction and Cell Death. Mol Neurobiol. 2016.

89.

Nonaka T, Hasegawa M. A cellular model to monitor proteasome dysfunction by alpha-synuclein. Biochemistry. 2009;48(33):8014–22.PubMedPubMedCentralCrossRef

90.

Kondo K, Obitsu S, Teshima R. α-Synuclein aggregation and transmission are enhanced by leucine-rich repeat kinase 2 in human neuroblastoma SH-SY5Y cells. Biol Pharm Bull. 2011;34(7):1078–83.PubMedCrossRef

91.

Al-Ali H, Blackmore M, Bixby JL, Lemmon VP. High Content Screening with Primary Neurons. 2014.

92.

Shi Z, Lu Z, Zhao Y, Wang Y, Zhao-Wilson X, Guan P, et al. Neuroprotective effects of aqueous extracts of Uncaria tomentosa: Insights from 6-OHDA induced cell damage and transgenic Caenorhabditis elegans model. Neurochem Int. 2013;62(7):940–7.PubMedCrossRef

93.

Johnson WM, Golczak M, Choe K, Currran PL, Miller OG, Yao C, et al. Regulation of DJ-1 by glutaredoxin 1 in vivo – implications for Parkinson’s disease. Biochemistry. 2016;55(32):4519–32.PubMedPubMedCentralCrossRef

94.

Greene LA, Tischler AS. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A. 1976;73(7):2424.PubMedPubMedCentralCrossRef

95.

Westerink RHS, Ewing AG. The PC12 cell as model for neurosecretion. Acta Physiol (Oxf). 2008;192(2):273.CrossRef

96.

Klebe RJ, Ruddle FH. Neuroblastoma: cell culture analysis of a differentiating stem cell system. J Cell Biol. 1969;43:69a.

97.

Tremblay RG, Sikorska M, Sandhu JK, Lanthier P, Ribecco-Lutkiewicz M, Bani-Yaghoub M. Differentiation of mouse Neuro 2A cells into dopamine neurons. J Neurosci Methods. 2010;186(1):60–7.PubMedCrossRef

98.

Choi HK, Won LA, Kontur PJ, Hammond DN, Fox AP, Wainer BH, et al. Immortalization of embryonic mesencephalic dopaminergic neurons by somatic cell fusion. Brain Res. 1991;552(1):67–76.PubMedCrossRef

99.

Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, et al. Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell. 2009;136(5):964–77.PubMedPubMedCentralCrossRef

100.

Hartfield EM, Fernandes HJR, Vowles J, Cowley SA, Wade-Martins R, Liu X, et al. Cellular reprogramming: a new approach to modelling Parkinson’s disease. Biochem Soc Trans. 2012;40(5):1152–7.PubMedCrossRef

101.

Badger JL, Cordero-Llana O, Hartfield EM, Wade-Martins R. Parkinson’s disease in a dish – Using stem cells as a molecular tool. Neuropharmacology. 2014;76:88–96.PubMedCrossRef

102.

Blesa J, Przedborski S. Parkinson’s disease: animal models and dopaminergic cell vulnerability. Front Neuroanat. 2014;8:155.PubMedPubMedCentralCrossRef

103.

Jagmag SA, Tripathi N, Shukla SD, Maiti S, Khurana S. Evaluation of Models of Parkinson’s Disease. Front Neurosci. 2015;9:503.PubMed

Title: The SH-SY5Y cell line in Parkinson’s disease research: a systematic review
Authors: Helena Xicoy
Bé Wieringa
Gerard J.M. Martens
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2017
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/s13024-017-0149-0

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

The SH-SY5Y cell line in Parkinson’s disease research: a systematic review

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2017

Gad67 haploinsufficiency reduces amyloid pathology and rescues olfactory memory deficits in a mouse model of Alzheimer’s disease

Phosphorylation of tau at Y18, but not tau-fyn binding, is required for tau to modulate NMDA receptor-dependent excitotoxicity in primary neuronal culture

Dissecting the role of non-coding RNAs in the accumulation of amyloid and tau neuropathologies in Alzheimer’s disease

Quantitative proteomic analysis of Parkin substrates in Drosophila neurons

A C9ORF72 BAC mouse model recapitulates key epigenetic perturbations of ALS/FTD

Depletion of adult neurogenesis exacerbates cognitive deficits in Alzheimer’s disease by compromising hippocampal inhibition