Environmental toxin interactions with genetic risks for Parkinson's disease

描述（由申请人提供）：本申请是根据NIH通知no - od -09-058“NIH宣布竞争性修订申请的恢复法案资金可用性”提交的。兴趣在于剖析农药暴露与过量胞质多巴胺（DA）之间的相互作用，作为特发性帕金森病（PD）的潜在危险因素。在父母资助中，NIEHS R01 ES015747，果蝇被用来确定通过囊泡单胺转运体（VMAT）对DA的隔离保护免受农药神经毒性的机制。这里的目的是利用果蝇来筛选增强VMAT功能的药物，从而可能作为新的神经保护剂。本研究还试图使用啮齿动物PD模型来确定病毒介导的VMAT过表达是否会在哺乳动物中对农药提供神经保护，并进一步测试已在果蝇中鉴定的药物的潜在神经保护作用。

DESCRIPTION (provided by applicant): This application is submitted in response to NIH Notice Number NOT-OD-09-058 " NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications". Interest resides in dissecting the interplay between pesticide exposure and excess cytosolic dopamine (DA) as potential risk factors for idiopathic Parkinson's disease (PD). In the parent grant, NIEHS R01 ES015747, Drosophila is being used to determine the mechanism by which sequestration of DA by the vesicular monoamine transporter (VMAT) protects against the neurotoxicity of pesticides. Here the intent is to use Drosophila to screen for drugs that potentiate VMAT function and may thus act as novel neuroprotective agents. This proposal also seeks to use a rodent model of PD to determine whether viral mediated over-expression of VMAT will provide neuroprotection against pesticides in mammals, and to further test the potential neuroprotective effects of drugs that have been identified with flies. PUBLIC HEALTH RELEVANCE: This proposal will create jobs for 2 post-doctoral fellows, arguably the backbone of all biomedical research in the U.S. It will also help to financially support 6 undergraduate students through their work in the laboratories. This will serve to enhance their education, retain students in the university who otherwise might not be able to afford to continue, encourage work in an environment that will facilitate their long-term goals, and promote spending in a critical population.