BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

• 批准号: 10702045
• 负责人: RANDY STRONG
• 金额: --
• 依托单位: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2030-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10702045
• 关键词: 4 hydroxynonenal; Acceleration; Affect; Age Months; Aldehydes; Alzheimer' s Disease; Area; Award; Behavioral; Brain; California; Clinical; Disease; Dopamine; Drug Metabolic Detoxication; Etiology; Excision; Exhibits; Exposure to; FDA approved; Farming Community; Functional disorder; Gait; Genetic Polymorphism; Human; Hydralazine; Impairment; Isoenzymes; Link; Lipid Peroxidation; Measures; Metabolism; Midbrain structure; Military Personnel; Mitochondria; Modeling; Motor; Mus; Mutation; Nerve Degeneration; Parkinson Disease; Patients; Performance; Peripheral; Persons; Pesticides; Pharmaceutical Preparations; Population; Reducing Agents; Research; Research Support; Risk; Role; Safety; Scientist; Testing; Therapeutic Agents; Tissues; Toxic Environmental Substances; Transgenic Organisms; United States; Veterans; Work; adduct; age related; age related neurodegeneration; aged; agricultural pesticide; aldehyde dehydrogenases; alpha synuclein; behavioral study; career; diagnostic biomarker; dopaminergic neuron; environmental agent; epidemiology study; human old age (65+); in vivo; military veteran; neurochemistry; neuropathology; neuroprotection; new therapeutic target; overexpression; preclinical study; prevent; sporadic Parkinson' s Disease; symptom treatment; therapeutic target

The etiology of Parkinson's disease (PD) is largely unknown. Preclinical and epidemiological studies provide a strong link between old age, prior exposure to pesticides and the increased risk of developing Parkinson's disease. This is of particular relevance to the VA because military personnel are often exposed to environmental toxins, including pesticides, during deployment. Moreover, the veteran population is older than the U.S. population and thus at increased risk. Recent evidence supports a role for elevated biogenic aldehydes in PD. The work proposed will not only help to elucidate the mechanisms underlying Parkinson's disease, but it will determine whether agents that lower biogenic aldehydes may be neuroprotective in Parkinson's disease. The test agent and potential alternatives are FDA-approved drugs for which there is abundant information on their safety and efficacy. Therefore, if these preclinical studies show efficacy in models of PD, then they may be more easily tested clinically.

帕金森氏病（PD）的病因在很大程度上是未知的。临床前和流行病学研究提供了 老年之间的牢固联系，事先接触农药以及发展帕金森氏症的风险增加 疾病。这与VA特别相关，因为军事人员经常暴露于环境 部署期间，包括农药在内的毒素。此外，退伍军人人口比美国年龄较大 人口，因此风险增加。最近的证据支持PD中升高生物醛的作用。 提出的工作不仅将有助于阐明帕金森氏病的机制，而且还将 确定降低生物醛的药物是否可能在帕金森氏病中具有神经保护作用。这 测试剂和潜在的替代方法是FDA批准的药物，其中有大量信息 安全与功效。因此，如果这些临床前研究显示在PD模型中的功效，那么它们可能会更 容易在临床上进行测试。

项目成果

DOPAL initiates αSynuclein-dependent impaired proteostasis and degeneration of neuronal projections in Parkinson's disease.

• DOI: 10.1038/s41531-023-00485-1
• 发表时间: 2023-03-25
• 期刊: NPJ PARKINSONS DISEASE
• 影响因子: 8.7
• 作者: Masato, Anna;Plotegher, Nicoletta;Terrin, Francesca;Sandre, Michele;Faustini, Gaia;Thor, Andrea;Adams, Stephen;Berti, Giulia;Cogo, Susanna;De Lazzari, Federica;Fontana, Camilla Maria;Martinez, Paul Anthony;Strong, Randy;Bandopadhyay, Rina;Bisaglia, Marco;Bellucci, Arianna;Greggio, Elisa;Dalla Valle, Luisa;Boassa, Daniela;Bubacco, Luigi
• 通讯作者: Bubacco, Luigi