Identifying Regulators of Degeneration due to Defective Mitochondrial DNA

项目主任/首席调查员(末位、第一位、中间)：郭明 项目摘要/摘要 神经退行性疾病影响着50%的85岁以上的人口。这个 包括阿尔茨海默氏症在内的大多数神经退行性疾病的最大危险因素 疾病就是衰老。线粒体DNA(MtDNA)突变的积累导致 细胞功能障碍，导致人类衰老，并可在与年龄相关的 阿尔茨海默氏症、帕金森氏症和石棺减少症等疾病。策略 减少mtDNA有害突变载量，提高mtDNA质量控制 可能会减少与年龄相关的神经退行性疾病的病理。我们 在果蝇有丝分裂后产生了独特的转基因工具 含有mtDNA混合缺失突变的组织(有害的 异质性模型)。我们的目标是使用这些系统和系统生物学方法来 识别导致抑制或增强基因和化合物的 线粒体DNA质量控制。 OMB编号0925-0001/0002(03/16修订版批准至2018年10月31日)页面续格式页面

Program Director/Principal Investigator (Last, First, Middle): Guo, Ming Project Summary/Abstract Neurodegenerative disorders affect 50% of the population over the age of 85. The strongest risk factor for most neurodegenerative disorders including Alzheimer’s disease is aging. Accumulation of mitochondrial DNA (mtDNA) mutations leads to cellular dysfunction, contributes to human aging and can be observed in age-related diseases such as Alzheimer’s disease, Parkinson’s disease and sarcopenia. Strategies that reduce the mtDNA deleterious mutation load and improve mtDNA quality control are likely to reduce the age-related pathologies of neurodegenerative diseases. We have generated unique transgenic tools in living Drosophila melanogaster post-mitotic tissues that contain engineered mixed mtDNA deletion mutations (deleterious heteroplasmy models). We aim to use these systems and system biology approaches to identify genes and compounds that lead to suppression or enhancement of the mitochondrial DNA quality control. OMB No. 0925-0001/0002 (Rev. 03/16 Approved Through 10/31/2018) Page Continuation Format Page