Environmental toxin interactions with genetic risks for Parkinson's disease

描述(由申请人提供)：本申请是为了响应NIH通知编号NOT-OD-09-058“NIH宣布恢复法案资金可用于竞争性修订申请”而提交的。人们感兴趣的是解剖农药暴露和过量胞浆多巴胺(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NIEHS R01 ES015747中，果蝇被用来确定囊泡单胺转运体(VMAT)对DA的隔离保护免受杀虫剂的神经毒性的机制。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。这项建议还试图使用帕金森病的啮齿动物模型来确定病毒介导的VMAT过度表达是否会在哺乳动物中提供针对杀虫剂的神经保护，并进一步测试已被确定为苍蝇的药物的潜在神经保护作用。 与公共健康相关：这项提案将为两名博士后研究员创造就业机会，他们可以说是美国所有生物医学研究的中坚力量。它还将帮助资助6名本科生通过他们在实验室的工作。这将有助于加强他们的教育，留住原本可能负担不起继续教育的学生，鼓励他们在有助于实现长期目标的环境中工作，并促进关键人口的消费。

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.