4 iron-4 sulfur Clusters in Aging and Alzheimers Disease

4 铁-4 硫簇在衰老和阿尔茨海默病中的作用

• 批准号: 6437908
• 负责人: VALTER D. LONGO
• 金额: $ 9.53万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6437908
• 关键词: Alzheimer's disease; NAD(P)H dehydrogenase; PC12 cells; aconitate hydratase; aerobiosis; aging; amyloid proteins; creatine kinase; electron spin resonance spectroscopy; enzyme activity; enzyme linked immunosorbent assay; fluorescence spectrometry; genetically modified animals; histochemistry /cytochemistry; immunoprecipitation; iron sulfur protein; laboratory mouse; magnetic resonance imaging; neurons; oxidative stress; statistics /biometry; succinate dehydrogenase; superoxides; tissue /cell culture; western blottings

DESCRIPTON (Provided by applicant): The candidate was trained as a biochemist at UCLA where he specialized in studies of oxidative damage in yeast. Dr. Longo has spent the past three years as a PI of a funded yeast laboratory and as a Research Associate/Assistant Professor working on Alzheimer?s Disease-related projects. The candidate?s long-term career goals are to be a faculty member in a neuroscience program and to continue research on aging. He is applying for the K01 Award in Aging to develop his research skills and knowledge in the neuroscience field with particular focus on the fundamental mechanisms of oxidative damage in aging and neurodegenerative diseases. Dr. Caleb. Finch, Prof. of Gerontology, Neuroscience, and Molecular Biology at the Andrus Gerontology Center, will act as Dr. Longo?s mentor along with Prof. Kelvin Davies. The international stature of these faculty members in the field of aging, oxidative stress, and neurodegenerative diseases, make this environment ideal for the development of Dr. Longo expertise in these fields. Dr Longo will participate in the bimonthly chalk talks in the Neurobiology and Endocrinology of Aging, will attend the weekly research seminars and journal clubs in USC?s multidisciplinary neuroscience program, and will attend a course on the responsible conduct of research. The candidate will also be exposed to clinical studies on cognitive changes during normal aging and during Alzheimer disease (AD). The research project "4 Iron-4 Sulfur Clusters in Aging and Alzheimer?s Disease" proposes to test the hypothesis that the 4Fe-4S clusters, contained in certain dehydratase enzymes sensitive to superoxide toxicity, are a major source of the redox-active iron that mediates oxidative damage during aging and in Alzheimer?s Disease. This hypothesis will be tested by measuring redox-active iron in animal models for AD and by determining the contribution of 4Fe-4S clusters to the pool of redox-active iron and to oxidative damage and death in neurons and neuronal cell lines exposed to oxidants and beta amyloid.

描述(由申请人提供)：应聘者受过生物化学家培训 在加州大学洛杉矶分校，他专门研究酵母中的氧化损伤。Dr。 在过去的三年里，朗戈一直是一家资助的酵母实验室的私募股权投资公司 作为研究助理/助理教授研究阿尔茨海默病？S病相关问题 项目。候选人？S长期的职业目标是当一名教员 成为神经科学项目的成员，并继续研究衰老问题。他是 申请K01老龄奖，以发展他的研究技能和 神经科学领域的知识，特别关注基础知识 衰老和神经退行性疾病中氧化损伤的机制。Dr。 凯勒。芬奇，老年学、神经科学和分子生物学教授 安德鲁斯老年学中心将与S教授共同担任隆戈博士、S教授的导师。 凯尔文·戴维斯。这些教职员工在该领域的国际地位 衰老、氧化应激和神经退行性疾病，使这一点 为发展隆戈博士在这些领域的专业知识提供了理想的环境。 朗戈博士将参加每两个月一次的《神经生物学和 老年内分泌学，将参加每周的研究研讨会和期刊 参加南加州大学S多学科神经科学项目的俱乐部，并将参加一个 负责任的研究行为课程。候选人也将是 接触关于正常衰老和正常衰老过程中认知变化的临床研究 在阿尔茨海默病(AD)期间。4铁-4硫团簇研究项目 在衰老和阿尔茨海默病？S病？建议检验的假设是 4Fe-4S簇，包含在某些对 超氧化物毒性，是氧化还原活性铁的主要来源，它介导 衰老和阿尔茨海默病中的氧化损伤？S病。这一假说将 通过在AD动物模型中测量氧化还原活性铁和通过 确定4Fe-4S团簇对氧化还原活性池的贡献 铁与神经元和神经细胞系的氧化损伤和死亡 暴露在氧化剂和β淀粉样蛋白中。