Ubiquitin and Parkinson's disease through the looking glass of genetics

Walden, H. and Muqit, M. M.K. (2017) Ubiquitin and Parkinson's disease through the looking glass of genetics. Biochemical Journal, 474(9), pp. 1439-1451. (doi: 10.1042/BCJ20160498) (PMID:28408429) (PMCID:PMC5390927)

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Biochemical alterations found in the brains of Parkinson's disease (PD) patients indicate that cellular stress is a major driver of dopaminergic neuronal loss. Oxidative stress, mitochondrial dysfunction, and ER stress lead to impairment of the homeostatic regulation of protein quality control pathways with a consequent increase in protein misfolding and aggregation and failure of the protein degradation machinery. Ubiquitin signalling plays a central role in protein quality control; however, prior to genetic advances, the detailed mechanisms of how impairment in the ubiquitin system was linked to PD remained mysterious. The discovery of mutations in the α-synuclein gene, which encodes the main protein misfolded in PD aggregates, together with mutations in genes encoding ubiquitin regulatory molecules, including PTEN-induced kinase 1 (PINK1), Parkin, and FBX07, has provided an opportunity to dissect out the molecular basis of ubiquitin signalling disruption in PD, and this knowledge will be critical for developing novel therapeutic strategies in PD that target the ubiquitin system.

Item Type:Articles
Additional Information:Research in the H.W. laboratory is supported by Cancer Research UK [grant number 17739] and the Medical Research Council (MRC) [grant number MC_UU_12016/12]. The M.M.K.M laboratory is supported by the Wellcome Trust [101022/Z/13/Z], MRC, Parkinson’s UK, Michael J. Fox Foundation for Parkinson’s disease research, J Macdonald Menzies Charitable Trust, an EMBO-YIP, and the Biotechnology and Biological Sciences Research Council.
Glasgow Author(s) Enlighten ID:Walden, Professor Helen
Authors: Walden, H., and Muqit, M. M.K.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Biochemical Journal
Publisher:Portland Press Ltd.
ISSN (Online):1470-8728
Published Online:13 April 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Biochemical Journal 474(9):1439-1451
Publisher Policy:Reproduced under a Creative Commons License

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