title: The role of autophagy in Parkinson's disease: rotenone-based modeling.
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.
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, Hubei, 430022, China.
authors.forename: Nian
authors.initials: N
authors.lastname: Xiong
authors.forename: Jing
authors.initials: J
authors.lastname: Xiong
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Chen
authors.forename: Jinsha
authors.initials: J
authors.lastname: Huang
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Lingling
authors.initials: L
authors.lastname: Hou
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Luo
authors.forename: Devina
authors.initials: D
authors.lastname: Ghoorah
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Lin
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D016923:Cell Death; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone; D013778:Tetrazolium Salts; D013844:Thiazoles; D014475:Uncoupling Agents
chemical_list: D004396:Coloring Agents; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D014475:Uncoupling Agents; D012402:Rotenone; C022616:thiazolyl blue