›› 2019, Vol. 39 ›› Issue (3): 239-.doi: 10.3969/j.issn.1674-8115.2019.03.004

• Original article (Basic research) • Previous Articles     Next Articles

Effects of chaperone-mediated autophagy on the level of α-synuclein oligomers in Parkinsons disease cell model

YANG Xiao1, DU Yun-lan1, BAI Xue-feng2, ZHU De-sheng1, WANG Fei1, HAN Lu1, GUAN Yang-tai1   

  1. 1. Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; 2. Pediatric Translational Medicine Institute, Shanghai Childrens Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Online:2019-03-28 Published:2019-04-28
  • Supported by:
    National Natural Science Foundation of China, 81671247; Natural Science Foundation of Shanghai,16ZR1420100

PDF (PC)

513

Abstract: Objective · To investigate the effects of chaperone-mediated autophagy (CMA) on α-synuclein oligomers level in the Parkinsons disease (PD) cell model with impaired ubiquitin proteasome system (UPS). Methods · The PD cell model was establishedadding 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 detectedimmunoprecipitation. 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 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.

Key words: Parkinsons disease (PD), &, alpha, -synuclein, oligomers, chaperone-mediated autophagy (CMA)

CLC Number: