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

Helen Walden (Lead / Corresponding author), Miratul M. K. Muqit (Lead / Corresponding author)

Research output: Contribution to journalReview article

13 Citations (Scopus)
169 Downloads (Pure)

Abstract

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.
Original languageEnglish
Pages (from-to)1439-1451
Number of pages13
JournalBiochemical Journal
Volume474
Issue number9
Early online date13 Apr 2017
DOIs
Publication statusPublished - May 2017

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