| Abstract No.: | 108 |
| Country: | Canada |
| | |
| Title: | MODELING PARKINSON DISEASE IN DROSOPHILA |
| | |
| Authors/Affiliations: | 1 Brian E. Staveley*;
1 Memorial University of Newfoundland, St. John's, NL, Canada
|
| | |
| Content: | Parkinson disease (PD), the most prevalent neurodegenerative movement disorder, is characterised by loss of the pigmented dopamine-producing neurons of the brain. As many genes associated with PD are conserved between humans and fruit flies, our laboratory investigates the common biological mechanisms disrupted in PD using the fly as a model organism.
Early, we demonstrated that the directed expression of the parkin gene (PARK2) rescues an alpha-synuclein induced Parkinson's disease-like phenotype in Drosophila, presumably through targeting the protein for degradation. Similar expression of PINK1 (PARK6) also rescues these phenotypes and suppresses alpha-synuclein induced developmental defects of the eye. Both parkin and PINK1 counteract the effects of an introduced "model" toxic protein. PINK1 is very effective in these activities and may control unidentified detoxification components in addition to parkin. In other work, we have identified the Drosophila homologue of Lrrk2 (PARK8) and show that lrrk mutants recapitulate the climbing defects of mutants in other PD gene homologues (such as parkin and PINK1). The lrrk mutants exhibit a number of phenotypes indicative of the disruption of the balance between neuromelanin and dopamine production that may lead to significant stresses. Our exploitation of the fruit fly as a model is advancing our knowledge of conserved mechanisms, including protein detoxification and the fine control of dopamine production, that appear to be fundamental to the biology of Parkinson disease.
Supported by: Memorial University's School of Graduate Studies, Parkinson Society Canada Friedman Pilot Project Grants and NSERC Discovery & Research Tools and Equipment Grants |
| | |
| Back |
|
