Pathologic and therapeutic implications for the cell biology of parkin

• Published in: Molecular and cellular neuroscience 2015-05, Vol.66 (Pt A), p.62-71
• Main Authors: Charan, Rakshita A., LaVoie, Matthew J.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Humans; Mitophagy; Molecular Targeted Therapy - methods; Mutation - genetics; Neurodegeneration; Parkin; Parkinson Disease - genetics; Parkinson Disease - pathology; Parkinson Disease - therapy; Therapy; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2015.02.008

Mutations in the E3 ligase parkin are the most common cause of autosomal recessive Parkinson's disease (PD), but it is believed that parkin dysfunction may also contribute to idiopathic PD. Since its discovery, parkin has been implicated in supporting multiple neuroprotective pathways, many revolving around the maintenance of mitochondrial health quality control and governance of cell survival. Recent advances across the structure, biochemistry, and cell biology of parkin have provided great insights into the etiology of parkin-linked and idiopathic PD and may ultimately generate novel therapeutic strategies to slow or halt disease progression. This review describes the various pathways in which parkin acts and the mechanisms by which parkin may be targeted for therapeutic intervention. This article is part of a Special Issue entitled ‘Neuronal Protein’. •Parkin biology is relevant to the etiology of familial and idiopathic PD.•There is a critical need to understand the full consequences of parkin deficiency.•Parkin regulates complex pathways of mitochondrial quality control and cell death.•Players in parkin biology may evolve to novel targets for therapeutic intervention.