title: The HtrA2 Drosophila model of Parkinson's disease is suppressed by the pro-survival Bcl-2 Buffy.
abstract: Mutations in High temperature requirement A2 (HtrA2), also designated PARK13, which lead to the loss of its protease activity, have been associated with Parkinson's disease (PD). HtrA2 is a mitochondrial protease that translocates to the cytosol upon the initiation of apoptosis where it participates in the abrogation of inhibitors of apoptosis (IAP) inhibition of caspases. Here, we demonstrate that the loss of the HtrA2 function in the dopaminergic neurons of Drosophila melanogaster results in PD-like phenotypes, and we attempt to restore the age-dependent loss in locomotor ability by co-expressing the sole pro-survival Bcl-2 homologue Buffy. The inhibition of HtrA2 in the dopaminergic neurons of Drosophila resulted in shortened lifespan and impaired climbing ability, and the overexpression of Buffy rescued the reduction in lifespan and the age-dependent loss of locomotor ability. In supportive experiments, the inhibition of HtrA2 in the Drosophila eye results in eye defects, marked by reduction in ommatidia number and increased disruption of the ommatidial array; phenotypes that are suppressed by the overexpression of Buffy.
authors.affiliation: Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.|Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.
authors.forename: P Githure
authors.initials: PG
authors.lastname: M'Angale
authors.affiliation: Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.|Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Staveley
mesh_terms: D000375:Aging / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D002470:Cell Survival / Q000235:genetics; D017124:Conserved Sequence; D004195:Disease Models, Animal; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D000074923:High-Temperature Requirement A Serine Peptidase 2; D008124:Locomotion / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D054731:PDZ Domains; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012697:Serine Endopeptidases; D000074923:High-Temperature Requirement A Serine Peptidase 2; C530280:HtrA2 protein, Drosophila
keywords: Buffy; Drosophila melanogaster; HtrA2; Maladie de Parkinson; PARK13; Parkinson disease; ageing; dopaminergic neurons; neurones dopaminergiques; vieillissement