Effects of chaperone-mediated autophagy on the level of α-synuclein oligomers in Parkinson's disease cell model
10.3969/j.issn.1674-8115.2019.03.004
- Author:
Xiao YANG
1
Author Information
1. Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine
- Publication Type:Journal Article
- Keywords:
Chaperone-mediated autophagy (CMA);
Oligomers;
Parkinson's disease (PD);
α-synuclein
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2019;39(3):239-243
- CountryChina
- Language:Chinese
-
Abstract:
Objective • To investigate the effects of chaperone-mediated autophagy (CMA) on α-synuclein oligomers level in the Parkinson's disease (PD) cell model with impaired ubiquitin proteasome system (UPS). Methods • The PD cell model was established by adding the proteasome inhibitor lactacystin in the SK-N-SH cell line stably transfected with wild type α-synuclein. The levels of α-synuclein oligomers, lysosome-associated membrane protein type 2A (LAMP2A) and 70 kDa heat shock homologous protein (HSC70) were detected using Western blotting. CMA function was inhibited with LAMP2A siRNA, and its effects on α-synuclein oligomers and cell viability were detected. Furthermore, the interaction of LAMP2A with α-synuclein oligomers was detected by immunoprecipitation. Results • In the PD cell model, the levels of α-synuclein oligomers, and CMA related proteins, i.e. LAMP2A and HSC70, were increased. Inhibiting the expression of LAMP2A further increased α-synuclein oligomers level, while it decreased cell viability. Furthermore, LAMP2A could interact with α-synuclein oligomers. Conclusion • In the PD cell model, CMA is one of the pathways regulating α-synuclein oligomers level. Inhibiting CMA function can further increase the α-synuclein oligomers level and deteriorate cell survival.
