Center for Gene Environment in Parkinson's Disease

帕金森病基因环境中心

• 批准号: 8292140
• 负责人: MARIE-FRANCOISE S CHESSELET
• 金额: $ 136.86万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8292140
• 关键词: Affect; Agriculture; Aldehydes; Animal Model; Basic Science; California; Cell Death; Cell model; Cessation of life; Collaborations; Disease; Drosophila genus; Drug Metabolic Detoxication; Environment; Enzymes; Epidemiology; Exposure to; Functional disorder; General Population; Genes; Genetic; Health; Human; Lead; Microtubules; Modeling; Molecular; Nerve Degeneration; Neurons; Parkinson Disease; Pathogenesis; Pathway interactions; Patients; Pesticides; Risk; Risk Factors; Rodent; System; Testing; Ubiquitin; aldehyde dehydrogenases; base; cohort; disorder risk; dopaminergic neuron; environmental agent; multicatalytic endopeptidase complex; neurotoxicity; novel; programs; research study; therapeutic target

The major theme of the UCLA CENTER FOR GENE ENVIRONMENT IN PARKINSON DISEASE (PD) is to identify novel mechanisms of pathogenesis for sporadic PD by understanding the primary cellular mechanisms by which agricultural pesticides that we and others have demonstrated to be risk factors for PD. produce dysfunction and death of dopamine neurons in cellular and animal models, and lead to PD in humans. Our group has begun to identify an association between exposure to specific pesticides and an increased risk for PD in an exceptionally well-characterized patient cohort in the agricultural region of California Central Valley. In parallel experiments, we have discovered that several of these pesticides affect specific cellular pathways potentially involved in PD. In particular, we have evidence that several agricultural pesticides associated with an increased risk of PD interfere with the ubiquitin-proteasome system (UPS). In addition to their effects on the proteasome, these pesticides to varying extent interfere with microtubule assembly, and/or inhibit aldehyde dehydrogenase, a key detoxification enzyme. The central hypothesis to be tested in the Center is that disruption of these particular cellular mechanisms by some agricultural pesticides is responsible for their ability to increase the risk of PD. Four integrated projects will combine human-based studies in a unique epidemiological cohort (project 4) with basic research studies in cellular (project 1), Drosophila (project 2) and rodent (project 3) models. We expect that the results of our studies will identify novel molecular pathways involved in neurodegeneration in PD, and specific therapeutic targets to stop or reverse the course of the disease. In addition, a better understanding of the potential neurotoxicity of widely used pesticides will have implications for their use in the environment to protect the health of workers and the general population, who are exposed to environmental pesticides in or near agricultural settings.

加州大学洛杉矶分校帕金森病（PD）基因环境研究中心的主要主题是

项目成果

Effects of decreased dopamine transporter levels on nigrostriatal neurons and paraquat/maneb toxicity in mice.

• DOI: 10.1016/j.neurobiolaging.2016.11.015
• 发表时间: 2017-03
• 期刊: Neurobiology of aging
• 影响因子: 4.2
• 作者: Richter F;Gabby L;McDowell KA;Mulligan CK;De La Rosa K;Sioshansi PC;Mortazavi F;Cely I;Ackerson LC;Tsan L;Murphy NP;Maidment NT;Chesselet MF
• 通讯作者: Chesselet MF