Redox regulation of protein functions linked to neurodegeneration

项目摘要/摘要： 神经退行性变过程中出错的分子和代谢机制 人们对此仍然知之甚少。一种名为ataxin-2的保守蛋白质被认为与 多聚谷氨酰胺束扩张引起的神经变性可影响 自身和其他蛋白质的聚集。然而，这种蛋白质的正常功能和 它们改变的后果尚不清楚。最近的研究表明，这种蛋白质 可以作为氧化还原传感器，通过某种方式调节细胞新陈代谢和信号 以维持线粒体的健康和细胞的存活率。该提案将调查以下几个方面 在酵母和哺乳动物细胞中，ataxin-2感受氧化还原的机制， 下游产出，以及突变和变异对相关的后果 细胞功能。

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.