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

• 批准号: 10302940
• 负责人: Benjamin P Tu
• 金额: $ 7.27万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 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/10302940
• 关键词: Cell physiology; Cells; Health; Link; Mammalian Cell; Metabolic; Metabolism; Mitochondria; Molecular; Mutation; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Output; Oxidation-Reduction; Proteins; Regulation; SCA2 protein; Signal Transduction; Therapeutic; Variant; Yeasts; innovation; insight; mitochondrial dysfunction; polyglutamine; protein function; sensor; treatment strategy

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。