Journal
BEHAVIORAL AND BRAIN FUNCTIONS
Volume 9, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1744-9081-9-13
Keywords
Autophagy; LC3; Parkinson's Desease; Rotenone; Autophagosome; Pathogenesis
Categories
Funding
- National Natural Science Foundation of China [30870866, 81071021, 31171211, 81200983, 81100958]
- Wuhan Science and Technology Bureau, China [20066002100]
- China Medical Foundation [2012B09]
Ask authors/readers for more resources
Background: Autophagy-mediated self-digestion of cytoplasmic inclusions may be protective against neurodegenerative diseases such as Parkinson's disease (PD). However, excessive autophagic activation evokes autophagic programmed cell death. Methods: In this study, we aimed at exploring the role of autophagy in the pathogenesis of rotenone-induced cellular and animal models for PD. Results: Reactive oxygen species over-generation, mitochondrial membrane potential reduction or apoptosis rate elevation occurred in a dose-dependent fashion in rotenone-treated human neuroblastoma cell line SH-SY5Y. The time-and dose-dependent increases in autophagic marker microtubule-associated protein1 light chain 3 (LC3) expression and decreases in autophagic adaptor protein P62 were observed in this cellular model. LC3-positive autophagic vacuoles were colocalized with alpha-synuclein-overexpressed aggregations. Moreover, the number of autophagic vacuoles was increased in rotenone-based PD models in vitro and in vivo. Conclusions: These data, along with our previous finding showing rotenone- induced toxicity was prevented by the autophagy enhancers and was aggravated by the autophagy inhibitors in SH-SY5Y, suggest that autophagy contributes to the pathogenesis of PD, attenuates the rotenone toxicity and possibly represents a new subcellular target for treating PD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available