Environmental toxin interactions with genetic risks for Parkinson's disease

环境毒素与帕金森病遗传风险的相互作用

• 批准号: 7818366
• 负责人: David Evan Krantz
• 金额: $ 19.23万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-17 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7818366
• 关键词: Award; Biomedical Research; Brain; California; Cell Death; Cessation of life; Chronic; Contracts; Cytosol; Data; Dopamine; Drosophila genus; Education; Effectiveness; Environment; Epidemiology; Exposure to; Functional disorder; Funding; Funding Mechanisms; Genetic Risk; Genetic Screening; Goals; Homologous Gene; Human; Laboratories; Locomotion; Mammals; Mediating; Modeling; Mus; National Institute of Environmental Health Sciences; Neuroprotective Agents; Occupations; Paraquat; Parents; Parkinson Disease; Parkinsonian Disorders; Pesticides; Pharmaceutical Preparations; Population; Postdoctoral Fellow; Preclinical Drug Evaluation; Property; Protein Isoforms; Rattus; Recovery; Relative (related person); Risk; Risk Factors; Rodent; Rodent Model; Rotenone; Students; Substantia nigra structure; Synaptic Vesicles; Testing; Therapeutic; Time; Toxic Environmental Substances; Toxin; United States National Institutes of Health; Universities; Vertebral column; Viral; Woman; Work; alpha synuclein; base; dopaminergic neuron; drug candidate; fly; interest; mouse model; mutant; neuroprotection; neurotoxic; neurotoxicity; novel; parent grant; pesticide exposure; public health relevance; response; translational approach; vesicular monoamine transporter

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.

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。兴趣在于解剖农药暴露和过量的胞质多巴胺（DA）之间的相互作用，作为潜在的危险因素，特发性帕金森病（PD）。在NIEHS R01 ES 015747的母基金中，果蝇被用于确定囊泡单胺转运蛋白（VMAT）对DA的隔离保护免受农药神经毒性的机制。本研究的目的是利用果蝇筛选增强VMAT功能的药物，从而可能作为新的神经保护剂。该提案还试图使用PD的啮齿动物模型来确定病毒介导的VMAT过表达是否会在哺乳动物中提供针对农药的神经保护，并进一步测试已用苍蝇鉴定的药物的潜在神经保护作用。 公共卫生相关性：该提案将为2名博士后研究员创造就业机会，可以说是美国所有生物医学研究的支柱，它还将有助于通过他们在实验室的工作为6名本科生提供经济支持。这将有助于加强他们的教育，留住那些否则可能无法继续学习的学生，鼓励他们在有利于实现长期目标的环境中工作，并促进关键人群的支出。