Pink1 suppresses α-synuclein-induced phenotypes in a Drosophila model of Parkinson’s disease
Parkinson’s disease (PD) is the most prevalent human neurodegenerative movement disorder and is characterized by a selective and progressive loss of the dopaminergic neurons. Mutations in the genes parkin and PTEN-induced putative kinase 1 (PINK1) result in autosomal recessive forms of PD. It has been suggested that parkin and Pink1 function in the same pathway in Drosophila , with Pink1 acting upstream of parkin. Previous work in our laboratory has shown the ability of parkin to rescue an α-synuclein-induced PD-like phenotype in Drosophila. To investigate the ability of Pink1 to protect against α-synuclein-induced toxicity, we have performed longevity, mobility, and histological studies to determine whether Drosophila Pink1 can rescue the α-synuclein phenotypes. We have found that overexpression of Pink1 results in the rescue of the α-synuclein-induced phenotype of premature loss of climbing ability, suppression of degeneration of the ommatidial array, and the suppression of α-synuclein-induced developmental defects in the Drosophila eye. These results mark the first demonstration of Pink1 counteracting PD phenotypes in a protein toxicity animal model, and they show that Pink1 is able to impart protection against potentially harmful proteins such as α-synuclein that would otherwise result in cellular stress.