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Identifying Regulators of Degeneration due to Defective Mitochondrial DNA

识别由于线粒体 DNA 缺陷引起的退化调节因子

基本信息

批准号：
10450087
负责人：
MING GUO
金额：
$ 75.73万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10450087
关键词：
Adult Affect Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease model Alzheimer&apos s disease pathology Amyloid beta-Protein Autophagocytosis Biological Biological Assay Brain Cells Cessation of life DNA Damage Deletion Mutation Disease Disease model Drosophila genus Drosophila melanogaster Drug Screening Drug Targeting Engineering Excision Eye FDA approved Financial compensation Free Radicals Functional disorder Gene Expression Gene Expression Profile Gene Expression Profiling Genes Genetic Transcription Genome Goals Human Intervention Knowledge Lead Mitochondria Mitochondrial DNA Mitotic Modeling Molecular Muscle Mutate Mutation Nerve Degeneration Nervous system structure Neurodegenerative Disorders Neuronal Dysfunction Neurons Organelles Oxidative Phosphorylation PINK1 gene Parkin Parkinson Disease Pathogenesis Pathology Pathway Analysis Pathway interactions Pharmaceutical Preparations Play Population Principal Investigator Production Public Health Quality Control RNA Interference Reporter Resources Risk Factors Role Screening Result Source System Systems Biology Tauopathies Testing Tissues Transgenic Model Transgenic Organisms age related age related neurodegeneration age-related muscle loss base cell type experimental study feeding frailty gain of function gene network genome wide screen genome-wide heteroplasmy improved in vivo insight loss of function mitochondrial DNA mutation mitochondrial dysfunction mitochondrial genome muscle degeneration mutant overexpression programs public health relevance response sarcopenia tau Proteins tau expression tool

项目摘要

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

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