Redox regulation of protein functions linked to neurodegeneration

与神经变性相关的蛋白质功能的氧化还原调节

基本信息

批准号：
10474399
负责人：
Benjamin P Tu
金额：
$ 35.88万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-25 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10474399
关键词：
Affect Amyotrophic Lateral Sclerosis Antibodies Antisense Oligonucleotides Autophagocytosis Binding Proteins Biochemical Biological Assay Biological Markers Biology Brain Cell Death Cell Line Cell physiology Cells Coupled Development Glean Growth Health Human Hydrogen Peroxide Individual Knowledge Lead Link Mammalian Cell Mass Spectrum Analysis Mediating Metabolic Metabolism Methionine Methods Mitochondria Molecular Motor Neurons Mus Mutate Mutation Mutation Analysis Nerve Degeneration Neurodegenerative Disorders Neurons Orthologous Gene Output Oxidation-Reduction Oxidative Stress Oxides Pathology Phase Phenotype Protein Engineering Protein Footprinting Proteins RNA RNA Recognition Motif RNA-Binding Proteins Regulation Reporter Respiration SCA2 protein Signal Transduction Spinocerebellar Ataxias Stress Therapeutic Tissue Sample Variant Water Yeasts experimental study improved innovation insight interest metabolomics mitochondrial dysfunction mutant novel overexpression oxidation polyglutamine protein TDP-43 protein function recruit respiratory response sensor stress granule therapeutic target treatment strategy

项目摘要

Project Summary/Abstract: The molecular and metabolic mechanisms that go awry during the course of neurodegeneration remain poorly understood. A conserved protein called ataxin-2 has been linked to neurodegeneration due to the occurrence of polyglutamine tract expansions that can influence the aggregation of itself and other proteins. However, the normal functions of this protein and the consequences of their alteration have not been clear. It was recently shown that the protein can function as a redox sensor to then regulate cellular metabolism and signaling in a manner that sustains mitochondrial health and cell survivability. This proposal will investigate aspects of the mechanism of redox sensing by ataxin-2 in both yeast and mammalian cells, the downstream outputs, as well as the consequences of mutations and variants on associated cellular functions.

项目摘要/摘要：神经退行性过程中出现问题的分子和代谢机制保持不当理解。一种称为ataxin-2的保守蛋白已与由于发生多谷氨酰胺的膨胀而导致的神经变性自身和其他蛋白质的聚集。但是，该蛋白质的正常功能和他们改变的后果尚不清楚。最近显示蛋白质可以用作氧化还原传感器，然后以某种方式调节细胞代谢和信号传导维持线粒体健康和细胞生存能力。该建议将调查酵母菌和哺乳动物细胞中共生2的氧化还原传感的机理，下游输出以及突变和变体对相关的后果细胞功能。