Validation of an In-Vitro Parkinson’s Disease Model for the Study of Neuroprotection

Proceedings

Tunahan Çakır¹  Esra Nur Yiğit²  Işıl Aksan Kurnaz²  Melis Savaşan Söğüt²  Ekin Sönmez² 

[1] Department of Bioengineering, Gebze Technical University, 41400 Kocaeli, Turkey;Department of Biotechnology, Gebze Technical University, 41400 Kocaeli, Turkey;

关键词: Parkinson’s disease;    SH-SY5Y;    α-synuclein;    A53T;    6-hydroxidopamine;   

DOI  :  10.3390/proceedings2251559

来源: DOAJ

【 摘 要 】

Parkinson’s disease (PD) is the second most common neurodegenerative disease with an estimation of 10 million people living with the disease and it is increasing in prevalence every year. Familial cases of PD are source of valuable information to determine genetical risk factors yet sporadic cases can emerge from distinct mechanisms so, identifying common pathways of familial and sporadic cases of PD may provide worthwhile insights to determine underlying mechanisms through the progression. LRRK2 mutations are the most common indicators of both sporadic and familial cases of PD and α-synuclein aggregation is one of the hallmarks of both cases of PD as well as in other synucleinopathies. As in the case of most neurological diseases, human studies addressing the molecular basis of pathology are generally restricted to post-mortem materials. For this reason, cell culture systems and animal models are widely used. There are two main approaches for modelling PD: genetically constructed PD models and neuroxin-based models. In this study, we aim to construct and compare both approaches by overexpressing wild-type (WT) and A53T mutant α-synuclein and treating cells with well-known neurotoxin 6-hydroxidopamine (6-OHDA) using dopaminergic human neuroblastoma SH-SY5Y cell line. Our findings suggest that WT or A53T α-synuclein overexpression by itself is not sufficient to cause significant toxicity in SH-SY5Y cells in the presented time scale. As expected, 6-OHDA treatment caused toxicity with an IC50 value of ~100 µM. In addition, 6-OHDA treatment causes 3- and 2.5-fold increase in SNCA and LRRK2 expression respectively.

【 授权许可】

Unknown