title: Deletion in exon 5 of the SNCA gene and exposure to rotenone leads to oligomerization of α-synuclein and toxicity to PC12 cells.
abstract: α-Synuclein (α-syn) is a presynaptic protein that is widely implicated in the pathophysiology of Parkinson's disease (PD). Recently, four α-syn isoforms that are produced by alternative splicing have been described, they are α-syn140, α-syn126, α-syn112, and α-syn98. The stable cell lines which expressed the four α-syn isoforms respectively were obtained, and the aggregation formation of these α-syn isoforms and their associated toxicity to PC12 cell were investigated. The results of this study indicate that over-expression of α-syn isoforms alone in dopaminergic cells have no effect on the formation of α-syn oligomeric species and cell viabilities. When exposed to rotenone, these cell lines which over expressed exon 5-lacking form of α-syn isoforms showed the formation of oligomeric species and toxicity to PC12 cells.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Ma
authors.forename: Lian-Kun
authors.initials: LK
authors.lastname: Song
authors.forename: Whitney Annie
authors.initials: WA
authors.lastname: Long
authors.forename: Yu-He
authors.initials: YH
authors.lastname: Yuan
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiu-Yun
authors.initials: XY
authors.lastname: Song
authors.forename: Fei
authors.initials: F
authors.lastname: Niu
authors.forename: Ning
authors.initials: N
authors.lastname: Han
authors.forename: Nai-Hong
authors.initials: NH
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D007306:Insecticides / Q000494:pharmacology*; D008958:Models, Molecular; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012402:Rotenone / Q000494:pharmacology*; D017384:Sequence Deletion / Q000235:genetics*; D014162:Transfection; D051844:alpha-Synuclein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D007306:Insecticides; D020033:Protein Isoforms; C497606:Snca protein, rat; D051844:alpha-Synuclein; D012402:Rotenone