Human Molecular Genetics - cover image from Whitworth Lab

Superoxide dismutating molecules rescue the toxic effects of PINK1 and parkin loss

An image from the latest article from our Mitochondrial Neurodegeneration research group, led by Dr Alex Whitworth, has been selected for the cover of the May issue of Human Molecular Genetics.

Lay Summary

Mitochondria, the energy factories of the cell, produce potentially toxic by-products of respiration termed ‘reactive oxygen species’ (ROS). Increased ROS and resulting oxidative stress has been linked to multiple neurodegenerative diseases such as Parkinson’s disease. In this study we investigated whether oxidative stress contributes to cell death in cellular and fruit fly models of Parkinson’s disease which recapitulate loss of PINK1 or parkin seen in some Parkinson’s patients. Using ROS sensors we found elevated mitochondrial ROS levels when PINK1 or parkin were mutated which impacted on mitochondrial fitness in cells and neuromuscular function in flies. These deficits could be reversed by increased expression of antioxidant enzymes (SODs) and also by treatment with a SOD-mimetic compound, M40403. These results support the further exploration of SOD-mimetic compounds as a possible therapeutic strategy for Parkinson’s disease.