Parkin function in Parkinson's disease

Arkinson, C. and Walden, H. (2018) Parkin function in Parkinson's disease. Science, 360(6386), pp. 267-268. (doi: 10.1126/science.aar6606) (PMID:29674580)

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease, and is characterized by involuntary shaking, muscle rigidity, and the progressive loss of dopaminergic neurons. In ∼5 to 10% of PD cases there is a genetic association, with almost 20 genes attributed to date. One example is early-onset autosomal recessive PD (ARPD), for which the majority of cases are linked to mutations in the Parkin gene (PRKN; also known as PARK2). PRKN encodes the E3 ubiquitin ligase Parkin, which plays important roles in mitochondrial quality control and turnover. Parkin, although localized to the mitochondria under certain conditions, is primarily cytosolic (1). A second ARPD-associated gene, PINK1 (PTEN-induced putative kinase 1), encodes a mitochondrially tethered kinase that regulates Parkin activity through phosphorylation events. Mutations in PINK1, although rare, are associated with a phenotype similar to that of ARPD patients with PRKN mutations. Numerous mutations throughout PRKN are linked to ARPD, making the functional examination of Parkin crucial to understanding ARPD pathogenesis. A wealth of structural studies have transformed our knowledge of Parkin regulation and catalytic mechanisms. However, the current picture is incomplete, leading to several possible models of Parkin catalysis, which has implications for understanding how the ARPD-associated mutations affect the protein and thus PD pathogenesis.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Arkinson, Connor and Walden, Professor Helen
• Authors: Arkinson, C., and Walden, H.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Science
• Publisher: American Association for the Advancement of Science
• ISSN: 0036-8075
• ISSN (Online): 1095-9203
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Science 360(6386): 267-268
• Publisher Policy: Reproduced in accordance with the publisher copyright policy