Induction of neuronal cell death by Rab5A-dependent endocytosis of α-synuclein

被引：166

作者：

Sung, JY

Kim, J

Paik, SR

Park, JH

Ahn, YS

Chung, KC

机构：

[1] Yonsei Univ, Coll Med, Dept Pharmacol, Seoul 120752, South Korea

[2] Yonsei Univ, Coll Med, Brain Res Inst, Seoul 120752, South Korea

[3] Yonsei Univ, Coll Med, Dept Microbiol, Seoul 120752, South Korea

[4] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul 120752, South Korea

[5] Inha Univ, Dept Biochem, Coll Med, Inchon 402751, South Korea

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2001年 / 276卷 / 29期

关键词：

D O I：

10.1074/jbc.M101318200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The presynaptic alpha -synuclein is a prime suspect for contributing to Lewy pathology and clinical aspects of diseases, including Parkinson's disease, dementia with Lewy bodies, and a Lewy body variant of Alzheimer's disease. Here we examined the pathogenic mechanism of neuronal cell death induced by alpha -synuclein. The exogenous addition of alpha -synuclein caused a marked decrease of cell viability in primary and immortalized neuronal cells. The neuronal cell death appeared to be correlated with the Rab5A-specific endocytosis of alpha -synuclein that subsequently caused the formation of Lewy body-like intracytoplasmic inclusions. This was further supported by the fact that the expression of GTPase-deficient Rab5A resulted in a significant decrease of its cytotoxicity as a result of incomplete endocytosis of alpha -synuclein.

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收藏

页码：27441 / 27448

页数：8

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