Biochemical analysis of the PINK1-parkin signalling pathway in Parkinson's disease

Parkinson's disease is an incurable neurodegenerative movement disorder whose incidence is set to increase in the coming decades. Spectacular genetic advances have uncovered nearly 20 genes or loci associated with the development of Parkinson's. For instance, autosomal recessive mutations in genes encoding a protein kinase, PINK1, and a ubiquitin ligase, parkin, are causative of early-onset forms of Parkinson's. Until recently little was known about the biochemical properties of these enzymes and how they are regulated. Dr Muqit has recently elucidated a signalling pathway in which PINK1 phosphorylates parkin at a highly conserved residue (serine 65) within its ubiquitin-like domain, and has demonstrated that this leads to the activation of parkin E3 ligase activity. He plans to investigate how this pathway is regulated and to determine how its disruption leads to neurodegeneration in Parkinson's. It is hoped that a greater mechanistic understanding of this pathway will lead to novel ideas for better diagnosis and treatment of Parkinson's.