The Role of Autophagy in Parkinson's Disease: Rotenone-Based Modeling

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The Role of Autophagy in Parkinson's Disease: Rotenone-Based Modeling

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Title: The Role of Autophagy in Parkinson's Disease: Rotenone-Based Modeling
Author: Xiong, Nian; Jia, Min; Zhang, Xiaowei; Chen, Zhenzhen; Huang, Jinsha; Zhang, Zhentao; Hou, Lingling; Luo, Zhijian; Ghoorah, Devina; Xiong, Jing; Liu, Ling; Lin, Zhicheng; Wang, Tao

Note: Order does not necessarily reflect citation order of authors.

Citation: Xiong, Nian, Jing Xiong, Min Jia, Ling Liu, Xiaowei Zhang, Zhenzhen Chen, Jinsha Huang, et al. 2013. The role of autophagy in Parkinson's disease: Rotenone-based modeling. Behavioral and Brain Functions 9(1): 13.
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Abstract: 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.
Published Version: doi:10.1186/1744-9081-9-13
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