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

Authors
 Jee Young Sung  ;  Jongsun Kim  ;  Seung R. Paik  ;  Jeon Han Park  ;  Young Soo Ahn  ;  Kwang Chul Chung 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.276(29) : 27441-27448, 2001 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2001
MeSH
Animals ; Cell Death/physiology* ; Cell Line ; Cytoplasm/ultrastructure ; Endocytosis* ; Nerve Tissue Proteins/metabolism* ; Neurons/cytology* ; Neurons/metabolism ; Rats ; Synucleins ; alpha-Synuclein ; rab5 GTP-Binding Proteins/genetics ; rab5 GTP-Binding Proteins/physiology*
Abstract
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.
Files in This Item:
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DOI
10.1074/jbc.M101318200
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jong Sun(김종선) ORCID logo https://orcid.org/0000-0002-3149-669X
Park, Jeon Han(박전한) ORCID logo https://orcid.org/0000-0001-9604-3205
Ahn, Young Soo(안영수)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141911
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