MPP+ impairs autophagic clearance of alpha-synuclein by impairing the activity of dynein

被引：37

作者：

Cai, Zeng-Lin ^{[1
,3
]}

Shi, Ji-Jun ^{[1
]}

Yang, Ya-Ping ^{[1
,2
]}

Cao, Bi-Yin ^{[1
]}

Wang, Feng ^{[1
]}

Huang, Jin-Zhong ^{[1
]}

Yang, Fang ^{[1
]}

Zhang, Ping ^{[1
]}

Liu, Chun-Feng ^{[1
,2
]}

机构：

[1] Soochow Univ, Affiliated Hosp 2, Dept Neurol, Suzhou 215004, Peoples R China

[2] Soochow Univ, Lab Aging & Nervous Dis, Suzhou 215004, Peoples R China

[3] Xuzhou Med Coll, Affiliated Lianyungang Hosp, Dept Neurol, Lianyungang, Peoples R China

来源：

NEUROREPORT | 2009年 / 20卷 / 06期

基金：

中国国家自然科学基金;

关键词：

1-methyl-4-phenylpyridinium; autophagy; dynein; LC3-II; Parkinson's disease; alpha-synuclein; NEUROBLASTOMA SH-SY5Y CELLS; PARKINSONS-DISEASE; NEURODEGENERATION; PHOSPHORYLATION; BIOCHEMISTRY; AGGREGATION; DEGRADATION; PROTEINS; DEATH;

D O I：

10.1097/WNR.0b013e32832986c4

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Increasing evidence suggests that dynein has an important role in the clearance of misfolded proteins by autophagy. Here we show that treatment of cells with 1-methyl-4-phenylpyridinium (MPP+) cause alpha-synuclein overexpression and aggregation, leading to the accumulation of autophagic vacuoles and the recruitment of LC3-II to these vacuoles in the cytoplasm. After MPP+ treatment dynein expression decreased and was mainly aggregated at the periphery of cytoplasm and lost its colocalization with alpha-synuclein and lamp1, indicating that dynein lost its function in the aggresome formation and failed to return autophagosome and lysosomes to the center of the cell for degradation. We consider that dynein plays an important role in the autophagic clearance of aggregate-prone proteins. NeuroReport 20:569-573 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

引用

页码：569 / 573

页数：5

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