Mitochondrial DNA Quality Control and Neurodegeneration

线粒体 DNA 质量控制和神经变性

基本信息

批准号：
8925935
负责人：
MING GUO
金额：
$ 30.8万
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：
2013
资助国家：
美国
起止时间：
2013-09-30 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8925935
关键词：
Adult Affect Age Aged, 80 and over Aging Alzheimer&apos s Disease Animals Autophagocytosis Biological Assay Brain Cell Culture System Cells Cessation of life DNA Damage Defect Disease Disease Progression Drosophila genus Drosophila melanogaster Drug Targeting Engineering Excision FDA approved Free Radicals Functional disorder Genes Genetic Screening Genome Goals Health Human Knowledge Lead Libraries Life Lipid Peroxidation Mammalian Cell Mitochondria Mitochondrial DNA Modeling Molecular Muscle Mutate Mutation Natural History Nerve Degeneration Nervous system structure Neurodegenerative Disorders Neurons Orthologous Gene Oxidative Phosphorylation PINK1 gene Parkinson Disease Pathology Pathway interactions Patients Phenotype Play Population Prevalence Production Proteins Public Health Quality Control Risk Factors Role Staging System Temperature Testing Tissues Work age related fly follow-up genetic analysis genome-wide genome-wide analysis high throughput screening improved in vivo insight loss of function mitochondrial DNA mutation mitochondrial dysfunction mitochondrial genome mutant parkin gene/protein prevent tool

项目摘要

DESCRIPTION (provided by applicant): Neurodegenerative disorders affect more than 50% of the population over the age of 80, and no treatment can halt the progression of the disease. The strongest risk factor for most, if not all, neurodegenerative disorders are aging. Accumulation of mitochondrial DNA (mtDNA) mutations is seen during human aging and leads to cellular dysfunction and death. Thus strategies that reduce the mtDNA load and improve mitochondrial DNA quality are likely to delay aging and reduce the age-related pathologies of neurodegenerative diseases. We have generated a unique tool in living Drosophila melanogaster that contains engineered mtDNA mutations. We aim to use these flies to carry out genome-wide genetic screens to identify those genes, when mutated, lead to suppression or enhancement of the mitochondrial quality control.

描述（由申请人提供）：神经退行性疾病影响超过 50% 的 80 岁以上人口，并且没有任何治疗可以阻止疾病的进展。大多数（如果不是全部）神经退行性疾病的最强危险因素是衰老。人类衰老过程中会出现线粒体 DNA (mtDNA) 突变的积累，并导致细胞功能障碍和死亡。因此，减少线粒体DNA负载和提高线粒体DNA质量的策略可能会延缓衰老并减少与年龄相关的神经退行性疾病病理。我们在活体果蝇中生成了一种独特的工具，其中包含工程化的 mtDNA 突变。我们的目标是利用这些果蝇进行全基因组遗传筛选，以识别这些基因，当突变时，会导致线粒体质量控制的抑制或增强。