The role of ubiquitin C-terminal hydrolase L1 in neurodegenerative disorders.
Impairment of the ubiquitin-proteasome system (UPS) results in the failure to remove and degrade misfolded proteins and consequently causes the accumulation of misfolded proteins in the cell. The aberrant interactions between misfolded proteins and normal intracellular proteins are thought to underlie the pathogenesis in many neurodegenerative diseases. Ubiquitin C-terminal hydrolase L1 (UCH-L1) is an important component of the UPS. Its major function is related to mono-ubiquitin recycling and thereby, sustaining protein degradation. Mutations of the UCH-L1 gene and alterations of its proteins' activity have been found to associate with several neurodegenerative disorders. In this review, we will discuss a link between UCH-L1 and Parkinson's, Huntington's and Alzheimer's diseases. We will also present a potential strategy for the treatment of Alzheimer's disease by boosting endogenous UCH-L1 activity.
Gong
Bing
B
Taub Institute for Research on Alzheimer's disease and the Aging Brain, Department of Pathology, Columbia University, New York, New York, USA. bg2058@columbia.edu
Leznik
Elena
E
D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D016503:Drug Delivery Systems; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*
C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex