Pink1 suppresses alpha-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 alpha-synuclein-induced PD-like phenotype in Drosophila. To investigate the ability of Pink1 to protect against alpha-synuclein-induced toxicity, we have performed longevity, mobility, and histological studies to determine whether Drosophila Pink1 can rescue the alpha-synuclein phenotypes. We have found that overexpression of Pink1 results in the rescue of the alpha-synuclein-induced phenotype of premature loss of climbing ability, suppression of degeneration of the ommatidial array, and the suppression of alpha-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 alpha-synuclein that would otherwise result in cellular stress.
Todd
Amy M
AM
Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B3X9 Canada.
Staveley
Brian E
BE
D000818:Animals; D030801:Animals, Genetically Modified; D019610:Cytoprotection / Q000235:genetics; D004195:Disease Models, Animal; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D005128:Eye Diseases / Q000151:congenital / Q000196:embryology / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics / Q000628:therapy*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D051844:alpha-Synuclein / Q000009:adverse effects*; D000099202:PTEN-Induced Putative Kinase
D029721:Drosophila Proteins; D017346:Protein Serine-Threonine Kinases; D051844:alpha-Synuclein; C534484:PINK1 protein, Drosophila; D000099202:PTEN-Induced Putative Kinase