Bcl-2 homologue Debcl enhances α-synuclein-induced phenotypes in Drosophila
| Autor: | Brian E. Staveley, P. Githure M’Angale |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Transgene Population lcsh:Medicine General Biochemistry Genetics and Molecular Biology Alpha-synuclein 03 medical and health sciences chemistry.chemical_compound Genetics education Gene Drosophila education.field_of_study biology General Neuroscience Dopaminergic lcsh:R General Medicine Cell Biology biology.organism_classification Phenotype Cell biology 030104 developmental biology Drosophila melanogaster chemistry Debcl Buffy General Agricultural and Biological Sciences Model of Parkinson disease Neuroscience |
| Zdroj: | PeerJ PeerJ, Vol 4, p e2461 (2016) |
| ISSN: | 2167-8359 |
| Popis: | BackgroundParkinson disease (PD) is a debilitating movement disorder that afflicts 1–2% of the population over 50 years of age. The common hallmark for both sporadic and familial forms of PD is mitochondrial dysfunction. Mammals have at least twenty proapoptotic and antiapoptoticBcl-2family members, in contrast, only twoBcl-2family genes have been identified inDrosophila melanogaster, the proapoptotic mitochondrial localizedDebcland the antiapoptoticBuffy. The expression of the human transgeneα-synuclein, a gene that is strongly associated with inherited forms of PD, in dopaminergic neurons (DA) of Drosophila, results in loss of neurons and locomotor dysfunction to model PD in flies. The altered expression ofDebclin the DA neurons and neuron-rich eye and along with the expression ofα-synucleinoffers an opportunity to highlight the role ofDebclin mitochondrial-dependent neuronal degeneration and death.ResultsThe directed overexpression ofDebclusing theDdc-Gal4transgene in the DA of Drosophila resulted in flies with severely decreased survival and a premature age-dependent loss in climbing ability. The inhibition ofDebclresulted in enhanced survival and improved climbing ability whereas the overexpression ofDebclin theα-synuclein-induced Drosophila model of PD resulted in more severe phenotypes. In addition, the co-expression ofDebclalong withBuffypartially counteracts theDebcl-induced phenotypes, to improve the lifespan and the associated loss of locomotor ability observed. In complementary experiments, the overexpression ofDebclalong with the expression ofα-synucleinin the eye, enhanced the eye ablation that results from the overexpression ofDebcl. The co-expression ofBuffyalong withDebcloverexpression results in the rescue of the moderate developmental eye defects. The co-expression ofBuffyalong with inhibition ofDebclpartially restores the eye to a roughened eye phenotype.DiscussionThe overexpression ofDebclin DA neurons produces flies with shortened lifespan and impaired locomotor ability, phenotypes that are strongly associated with models of PD in Drosophila. The co-expression ofDebclalong withα-synucleinenhanced the PD-like phenotypes. The co-expression ofDebclalong withBuffysuppresses these phenotypes. Complementary experiments in the Drosophila eye show similar trends during development. Taken all together these results suggest a role forDebclin neurodegenerative disorders. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|