This article is part of the supplement: Ubiquitin-Proteasome System in Disease Part 1
Role of the ubiquitin proteasome system in Parkinson's disease
1 Neurodegeneration Research Laboratory, National Neuroscience Institute, Singapore
2 Parkinson's Disease and Movement Disorders Center, National Neuroscience Institute, Singapore
3 Department of Biological Sciences, National University of Singapore, Singapore
BMC Biochemistry 2007, 8(Suppl 1):S13 doi:10.1186/1471-2091-8-S1-S13Published: 22 November 2007
Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Although a subject of intense research, the etiology of PD remains poorly understood. Recently, several lines of evidence have implicated an intimate link between aberrations in the ubiquitin proteasome system (UPS) and PD pathogenesis. Derangements of the UPS, which normally functions as a type of protein degradation machinery, lead to alterations in protein homeostasis that could conceivably promote the toxic accumulation of proteins detrimental to neuronal survival. Not surprisingly, various cellular and animal models of PD that are based on direct disruption of UPS function reproduce the most prominent features of PD. Although persuasive, new developments in the past few years have in fact raised serious questions about the link between the UPS and PD. Here I review current thoughts and controversies about their relationship and discuss whether strategies aimed at mitigating UPS dysfunction could represent rational ways to intervene in the disease.