作者
Youngah Shin, Jochen Klucken, Cam Patterson, Bradley T Hyman, Pamela J McLean
发表日期
2005/6/24
期刊
Journal of Biological Chemistry
卷号
280
期号
25
页码范围
23727-23734
出版商
Elsevier
简介
α-Synuclein is a major component of Lewy bodies, the pathological hallmark of Parkinson disease, dementia with Lewy bodies, and related disorders. Misfolding and aggregation of α-synuclein is thought to be a critical cofactor in the pathogenesis of certain neurodegenerative diseases. In the current study, we investigate the role of the carboxyl terminus of Hsp70-interacting protein (CHIP) in α-synuclein aggregation. We demonstrate that CHIP is a component of Lewy bodies in the human brain, where it colocalizes with α-synuclein and Hsp70. In a cell culture model, endogenous CHIP colocalizes with α-synuclein and Hsp70 in intracellular inclusions, and overexpression of CHIP inhibits α-synuclein inclusion formation and reduces α-synuclein protein levels. We demonstrate that CHIP can mediate α-synuclein degradation by two discrete mechanisms that can be dissected using deletion mutants; the …
引用总数
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Y Shin, J Klucken, C Patterson, BT Hyman, PJ McLean - Journal of Biological Chemistry, 2005