4 iron-4sulfur Clusters in Aging and Alzheimer's Disease

克莱顿（由申请人提供）：该候选人接受过生物化学家培训 在加州大学洛杉矶分校，他专门研究酵母的氧化损伤。博士 隆戈在过去的三年里一直担任一个受资助的酵母实验室的PI， 作为一个研究助理/助理教授工作在阿尔茨海默氏症？疾病相关 项目候选人？的长期职业目标是成为一名教师 神经科学计划的成员，并继续研究衰老。他是 申请K 01老化奖，以发展他的研究技能， 神经科学领域的知识，特别关注基础 衰老和神经退行性疾病中的氧化损伤机制。博士 凯勒布芬奇，老年学，神经科学和分子生物学教授， 安德鲁斯老年医学中心，将担任隆戈博士？的导师沿着教授。 凯文·戴维斯。这些教师在该领域的国际地位 衰老、氧化应激和神经退行性疾病， 环境非常适合Longo博士在这些领域的专业知识的发展。 隆戈博士将参加神经生物学的双月粉笔讲座， 衰老内分泌学，将参加每周的研究研讨会和期刊 南加州大学的俱乐部的多学科神经科学计划，并将参加一个 关于负责任地进行研究的课程。候选人还将 接触关于正常衰老期间认知变化的临床研究， 阿尔茨海默病（AD）。研究项目“4铁-4硫簇合物 老年痴呆症的研究吗“疾病”提出测试的假设， 4Fe-4S簇，包含在某些对 超氧化物毒性，是介导氧化还原活性铁的主要来源， 氧化损伤在老化和阿尔茨海默氏症？的疾病。这一假设将 通过测量AD动物模型中的氧化还原活性铁进行测试， 确定4Fe-4S簇对氧化还原活性池的贡献 铁和氧化损伤和死亡的神经元和神经元细胞系 暴露在氧化剂和β淀粉样蛋白中

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.