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Exp Neurol. 2005 Feb;191 Suppl 1:S17-27.

Ubiquitin-proteasome system and Parkinson's diseases.

Author information

1
Center for Neurodegenerative Disease, Department of Neurology, Emory University, Atlanta, GA 30322, USA. rbetarb@emory.edu

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by nigrostriatal dopaminergic degeneration and development of cytoplasmic inclusions known as Lewy bodies. To date, the mechanisms involved in PD pathogenesis are not clearly understood. Clues from genetic studies including identification of mutations in genes for alpha-synuclein, parkin, and ubiquitin carboxy hydrolase L1 associated with familial PD and the presence of proteinaceous cytoplasmic inclusions in spared dopaminergic nigral neurons in sporadic cases of PD have suggested an important role for ubiquitin-proteasome system (UPS) and aberrant protein degradation. In vivo and in vitro studies have linked parkin, alpha-synuclein, and oxidative stress to a compromised UPS and PD pathogenesis suggesting novel therapeutic targets.

PMID:
15629758
DOI:
10.1016/j.expneurol.2004.08.021
[Indexed for MEDLINE]

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