Role for the ubiquitin-proteasome system in Parkinson’s disease and other neurodegenerative brain amyloidoses

被引:0
|
作者
Darren J. Moore
Valina L. Dawson
Ted M. Dawson
机构
[1] Johns Hopkins University School of Medicine,Institute for Cell Engineering
[2] Johns Hopkins University School of Medicine,Department of Neurology
[3] Johns Hopkins University School of Medicine,Department of Neuroscience
[4] Johns Hopkins University School of Medicine,Department of Physiology
来源
NeuroMolecular Medicine | 2003年 / 4卷
关键词
Ubiquitin-proteasome system (UPS); Parkinson’s disease; Parkin; UCH-L1; α-synuclein; neurodegeneration; brain amyloidoses;
D O I
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中图分类号
学科分类号
摘要
Many neurodegenerative brain amyloidoses, including Alzheimer’s and Parkinson’s disease, are characterized by selective neuronal loss together with the appearance of intraneuronal ubiquitin-positive proteinaceous aggregates or inclusion bodies. These features usually result from the abnormal accumulation and processing of mutant, misfolded, or damaged intracellular proteins. It has recently become clear that both genetic factors and aberrant proteolytic degradation may therefore play a major role in neuronal degeneration. Indeed, the linkage of two genes directly involved in the ubiquitin-proteasome system (UPS) in familial Parkinson’s disease clearly indicates a central role for the UPS in neurodegeneration, and thus Parkinson’s disease is considered the prototypical disorder associated with UPS dysfunction. In this review, we provide an overview of the key genes / proteins implicated in the abnormal UPS-mediated proteolytic processing of unwanted proteins observed in neurodegenerative brain amyloidoses. We also provide an outline of the various components and pathways involved in the normal cellular functioning of the UPS and discuss the mechanisms by which UPS dysfunction can compromise neuronal integrity. A more complete understanding of the UPS and its relationship to the neurodegenerative process will undoubtedly provide tremendous insight into the molecular pathogenesis of amyloidogenic neurodegenerative disorders and will allow the development of novel rational therapies for treating these disorders.
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页码:95 / 108
页数:13
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