The HtrA2 Drosophila model of Parkinson’s disease is suppressed by the pro-survival Bcl-2 Buffy
| Autor: | P. Githure M’Angale, Brian E. Staveley |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Aging Parkinson's disease Cell Survival medicine.medical_treatment Gene Expression PDZ Domains 03 medical and health sciences 0302 clinical medicine Genetics medicine Animals Drosophila Proteins Amino Acid Sequence Molecular Biology Conserved Sequence Caspase Neurons Protease biology Serine Endopeptidases Dopaminergic Parkinson Disease General Medicine High-Temperature Requirement A Serine Peptidase 2 medicine.disease biology.organism_classification Phenotype Cell biology Disease Models Animal 030104 developmental biology Proto-Oncogene Proteins c-bcl-2 Apoptosis biology.protein Drosophila Drosophila melanogaster Locomotion 030217 neurology & neurosurgery Drosophila Protein Biotechnology |
| Zdroj: | Genome. 60:1-7 |
| ISSN: | 1480-3321 0831-2796 |
| DOI: | 10.1139/gen-2016-0069 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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