Mutant alpha-synuclein and autophagy in PC12 cells

作     者：Kangyong Liu Chunfeng Liu Chuancheng Ren Yaping Yang Liwei Shen Xuezhong Li Fen Wang Zhenghong Qin 

作者机构：Department of Neurology Fifth Hospital of Fudan University Shanghai 200240 China Department of Neurologyl Second Affiliated Hospital of Soochow University Suzhou 216005 Jiangsu Province China Laboratory of Aging and'Nervous Diseases Soochow University Suzhou 216005 Jiangsu Province China 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2011年第6卷第2期

页      面：91-95页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学] 071002[理学-动物学] 

基　　金：the National Natural Science Foundation of China,No. 30970869 a grant from Board of Health of Shanghai,China,No. 2008086 Youth Key Project in College of Medicine of Fudan University,No. 09-L37 a grant from the Project of Shanghai Key Laboratory of Diabetes Mellitus,No. 08DZ2230200 

主　　题：α-synuclein autophagy microtubule-associated protein light chain 3 Parkinson's disease: PC12 cells 

摘      要：Several studies have demonstrated that overexpression of mutant a-synuclein in PC12 cells is related to occurrence of autophagy. The present study established mutant α-synuclein （A30P） -transfected PC12 cells and treated them with the autophagy inducer rapamycin and autophagy inhibitor wortmannin, respectively. Results demonstrated that mutant a-synuclein resulted in cell death via autophagy and involved a-synuclein accumulation, membrane lipid oxidation, and loss of plasma membrane integrity. Mutant a-synuclein （A30P） also mediated toxicity of 1-methyl-4-phenylpyridinium ion. Moreover, rapamycin inhibited a-synuclein aggregation, while wortmannin promoted α-synuclein aggregation and cell death. To further determine the role of autophagy due to mutant α-synuclein, the present study measured expression of microtubule-associated protein light chain 3. Results revealed that wortmannin and 1-methyl-4-phenylpyridinium ion inhibited expression of microtubule-associated protein light chain 3 while rapamycin promoted its expression. These findings suggested that abnormal aggregation of a-synuclein induced autophagic programmed cell death in PC12 cells.