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Expert Rev Proteomics. 2007 Dec;4(6):769-81.

Ubiquitin-proteasome system dysfunction in Parkinson's disease: current evidence and controversies.

Author information

1
National Neuroscience Institute, Neurodegeneration Research Laboratory & Parkinson's Disease & Movement Disorders Center, 11 Jalan Tan Tock Seng, 308433, Singapore. kah_leong_lim@nni.com.sg

Abstract

Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Although a subject of intense research, the etiology of PD remains poorly understood. Over the last decade, the ubiquitin-proteasome system (UPS) has emerged as a compelling player in PD pathogenesis. Disruption of the UPS, which normally identifies and degrades intracellular proteins, is thought to promote the toxic accumulation of proteins detrimental to neuronal survival, thereby contributing to their demise. Support for this came from a broad range of studies, including genetics, gene profiling and post-mortem analysis, as well as in vitro and in vivo modeling. Notably, various cellular and animal models of PD based on direct disruption of UPS function reproduce the salient features of PD. However, several gaps remain in our current knowledge regarding the precise role of UPS dysfunction in the pathogenesis of the disease. Current thoughts regarding their relationship are reviewed here and some major unresolved questions, the clarification of which would considerably advance our understanding of the implicated role of the UPS in PD pathogenesis, are discussed.

PMID:
18067415
DOI:
10.1586/14789450.4.6.769
[Indexed for MEDLINE]

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