Expression of Bcl-2 homologues in the α-synuclein-induced Parkinson disease model in Drosophila

M'Angale, Peter Githure (2011) Expression of Bcl-2 homologues in the α-synuclein-induced Parkinson disease model in Drosophila. Masters thesis, Memorial University of Newfoundland.

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Abstract

In Parkinson disease (PD), the age-dependent degeneration of dopaminergic neurons (DA) and loss of locomotor function have been shown to be correlated with prominent mitochondrial abnormalities and dysfunction. A number of genes are associated with inherited forms of PD and most of these genes encode protein products that interact with components of the mitochondria. The pro-survival Bcl-2 proteins are reputed to be the guardians of the mitochondria, an organelle central to the process of cell death in all animals. Drosophila melanogaster possess two mitochondria localized Bcl-2-like proteins encoded by debel, which promotes cell death, and Buffy, which is pro-cell survival. The Bcl-2 proteins have been shown to have a dual role in the control of cell death and subsequent engulfment of cellular components (autophagy). In the α-synuclein-induced Drosophila model of PD, Buffy and debel were overexpressed in the DA neurons and developing eye using the UAS-GAL4 system of directed gene expression. Longevity and climbing ability of these flies were influenced by these two Bcl-2 genes: debel enhances the severity of the α-synuclein-induced age-dependent loss of climbing ability. On the other hand, Buffy suppresses the α-synuclein-induced PD-like phenotypes. When overexpressed in the developing neurons of the eye, a similar trend was observed with Buffy suppressing the eye defects. Taken together, these results suggest a protective role for Buffy, especially under α-synuclein-induced protein toxicity.

Item Type: Thesis (Masters)
URI: http://research.library.mun.ca/id/eprint/12268
Item ID: 12268
Additional Information: Includes bibliographical references (pages 70-81).
Department(s): Science, Faculty of > Biology
Date: September 2011
Date Type: Submission
Library of Congress Subject Heading: Apoptosis; Parkinson's disease--Animal models; Drosophila--Genetics; Homology (Biology)

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