Environmental Toxin Interactions with Genetic Risks for Parkinson’s DiseaseDavid. E. Krantz, M.D., Ph.D. Project DescriptionThe grant is focused on a unique Drosophila model to investigate gene-environment interactions related to Parkinson’s Disease. Specifically, the over-expression of the Drosophila vesicular monoamine transporter (DVMAT) is explored as protection against the neurotoxic effects of the mutated Parkin gene and two environmental toxins, rotenone and paraquat. This study will test the hypothesis that the neuroprotective effects of VMAT will extend to the neurotoxin paraquat, thought to act by a different mechanism than rotenone, and whether this requires its localization to synaptic vesicles. Experiments for gene-environment interactions will also be performed with the PD related gene, pink1, and established pink mutant phenotypes will be used to screen for agents that rescue the neurotoxic effects of mitochondrial dysfunction. |
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