DJ-1 and hexokinases

DJ-1 和己糖激酶

• 批准号: 9552524
• 负责人: Mark Cookson
• 金额: $ 21.14万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9552524
• 关键词: Bacteria; Brain; Cells; Clinical; Data; Event; Family; Genes; Goals; Human; Metabolic; Mitochondria; Molecular; Mus; Mutation; Oxidative Stress; PTEN gene; Parkinson Disease; Pathway interactions; Proteins; Rattus; Signal Pathway; Signal Transduction; age related; hexokinase; in vivo; interest; response

We have been interested in the relationship between oxidative stress and DJ-1, a rare cause of recessive Parkinson's disease, for several years and have focussed the relationship between oxidative stress and mitochondrial localization. In the current period, we have explored the effects of DJ-1 deficiency in the brains of mice and rats. We find that loss of DJ-1 alters cellular signaling pathways that result, at a cellular level, in the accumulation of changes in metabolic enyzmes. Our current data suggests that altered PTEN/Aky signaling occurs both in cells and in vivo as a consequence of DJ-1 deficiency. However, in vivo there are additional signaling events that occur downstream of Akt and we are subsequently trying to identify what these age-related pathways are.

多年来，我们一直对氧化应激与 DJ-1（隐性帕金森病的罕见病因）之间的关系感兴趣，并重点关注氧化应激与线粒体定位之间的关系。本期，我们探索了 DJ-1 缺陷对小鼠和大鼠大脑的影响。我们发现 DJ-1 的缺失会改变细胞信号传导途径，从而在细胞水平上导致代谢酶变化的积累。我们目前的数据表明，由于 DJ-1 缺陷，细胞和体内 PTEN/Aky 信号传导发生改变。然而，在体内，Akt 下游还发生其他信号传导事件，我们随后试图确定这些与年龄相关的途径是什么。