Of Parkin and Parkinson's: light and dark sides of a multifaceted E3 ubiquitin–protein ligase

Parkin mutations are the most frequent cause of autosomal recessive Parkinson's disease (PD). Parkin is an E3 ubiquitin–protein ligase initially thought to be involved in the ubiquitin–proteasome pathway but with emerging roles in a growing number of non-proteolytic processes. Genetics supports the idea that loss of Parkin function triggers disease. However, no unifying mechanism of loss of function has been identified, whereas intriguing data accumulate, suggesting that some parkin mutations confer toxicity to the encoded proteins. Although the molecular pathways of relevance to the pathogenesis of parkin-related Parkinson's disease remain mysterious, the pan-neuroprotective capacity of Parkin might be of therapeutic value.

Section editor:Graeme Bilde – Novartis Pharma, Basel, Switzerland