Induction of Neuronal Cell Death by Rab5A-dependent Endocytosis of α-Synuclein

Jee Young Sung, Jongsun Kim, Seung R. Paik, Jeon Han Park, Young Soo Ahn, Kwang Chul Chung

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

The presynaptic α-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 α-synuclein. The exogenous addition of α-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 α-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 α-synuclein.

Original languageEnglish
Pages (from-to)27441-27448
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number29
DOIs
Publication statusPublished - 2001 Jul 20

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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