title: Extracellular signal-regulated kinase is involved in alpha-synuclein-induced mitochondrial dynamic disorders by regulating dynamin-like protein 1.
abstract: Compounding evidence suggests that alpha-synuclein (SNCA) plays an important role in the pathogenesis of Parkinson's disease (PD) by inducing neurotoxicity. Mitochondria are highly dynamic organelles that undergo fusion and fission processes, the imbalance of which has been viewed as a key trigger for PD. However, the underlying relationship between SNCA and mitochondrial dynamics remains unclear. This study demonstrated that SNCA overexpression not only altered mitochondrial morphology, but also significantly increased the translocation of mitochondrial fission protein dynamin-like protein 1 (DLP1). To further investigate the mechanism of SNCA's effect on mitochondrial dynamics, the proteomic technique, stable isotope labeling of amino acid in cell cultures (SILAC), was used. The extracellular signal-regulated kinase (ERK) was confirmed to be involved in the regulation of DLP1 and SNCA-mediated neurotoxicity. Finally, additional results demonstrated that SNCA inducing both mitochondrial dynamic disorders and neurotoxicity could be ameliorated by curcumin through ERK inhibition, which implied that the agent could be used to prevent and treat PD in the future.
authors.affiliation: Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Ya-Xing
authors.initials: YX
authors.lastname: Gui
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Wang
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Kang
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Quinn
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Sheng-Di
authors.initials: SD
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D034281:Dynamins; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007554:Isotopes / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects* / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure*; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D053719:Tandem Mass Spectrometry; D014162:Transfection; D051844:alpha-Synuclein / Q000494:pharmacology*
chemical_list: D007554:Isotopes; D008869:Microtubule-Associated Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D051844:alpha-Synuclein; D049452:Green Fluorescent Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins