Bcl-2 homologue debcl enhances α-synuclein-induced phenotypes in Drosophila
- Published
- Accepted
- Subject Areas
- Cell Biology, Genetics
- Keywords
- debcl, Buffy, Drosophila melanogaster, alpha-synuclein, Model of Parkinson Disease
- Copyright
- © 2016 M'Angale et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2016. Bcl-2 homologue debcl enhances α-synuclein-induced phenotypes in Drosophila. PeerJ Preprints 4:e2025v1 https://doi.org/10.7287/peerj.preprints.2025v1
Abstract
Background Parkinson disease (PD) is a debilitating movement disorder that afflicts 1 to 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 antiapoptotic Bcl-2 family members, in contrast, only two Bcl-2 family genes have been identified in Drosophila melanogaster, the proapoptotic mitochondrial localized debcl and the antiapoptotic Buffy. The expression of α-synuclein, the first gene identified to contribute to inherited forms of PD, in the dopaminergic neurons (DA) of flies has provided a robust and well-studied Drosophila model of PD complete with the loss of neurons and accompanying motor defects. The altered expression of debcl in the DA neurons and neuron-rich eye and along with the expression of α-synuclein offers an opportunity to highlight the role of debcl in mitochondrial-dependent neuronal degeneration and death. Results The directed overexpression of debcl using the Ddc-Gal4 transgene in the dopaminergic neurons of Drosophila resulted in flies with severely decreased survival and a premature age-dependent loss in climbing ability. The inhibition of debcl resulted in enhanced survival and improved climbing ability whereas the overexpression of debcl in the α-synuclein-induced Drosophila model of PD resulted in more severe phenotypes. In addition, the co-expression of debcl along with Buffy partially counteracts the debcl-induced phenotypes, to improve the lifespan and the associated loss of locomotor ability observed. In complementary experiments, the overexpression of debcl along with the expression of α-synuclein in the eye, enhanced the eye ablation that results from the overexpression of debcl. The co-expression of Buffy along with debcl overexpression results in the rescue of the moderate developmental eye defects. The co-expression of Buffy along with inhibition of debcl partially restores the eye to a roughened eye phenotype. Discussion The overexpression of debcl in 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 of debcl along with α-synuclein enhanced the Parkinson disease-like phenotypes. The co-expression of debcl along with Buffy suppresses these phenotypes. Complementary experiments in the Drosophila eye show similar trends during development. Taken all together these results suggest a role for debcl in neurodegenerative disorders.
Author Comment
This is our research group's first submission to PeerJ for review.