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、先前接触杀虫剂与帕金森病风险增加之间存在密切联系 疾病这对退伍军人事务部特别重要，因为军事人员经常暴露在环境中， 部署期间的毒素，包括杀虫剂。此外，退伍军人的年龄比美国大。 人口，从而增加风险。最近的证据支持生物醛类升高在PD中的作用。 这项工作不仅有助于阐明帕金森病的潜在机制， 确定降低生物醛的药物是否可能对帕金森病具有神经保护作用。的 测试试剂和潜在替代物是FDA批准的药物， 安全有效。因此，如果这些临床前研究在PD模型中显示出有效性，那么它们可能更有价值。 很容易在临床上测试。

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