Targeting Redox-regulated Chaperone/Scaffold proteins as a therapeutic approach to prevent age-associated diseases

靶向氧化还原调节的伴侣/支架蛋白作为预防与年龄相关的疾病的治疗方法

• 批准号: 2884600
• 金额: --
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2884600
• 关键词: Targeting; Redox; regulated; Chaperone; Scaffold

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) have various biological sources and are generated as byproducts of oxygen metabolism. ROS cause damage that is linked to with various age-associated diseases including cancer. Hence, H2O2 is also employed as a signalling molecule to upregulate ROS defences by promoting the oxidation of specific cysteines in target signaling proteins. Our understanding of these signaling mechanisms is largely based on studies in yeast involving the addition of an H2O2 bolus to cells. Hence, it remains unclear how H2O2 reaches and reacts with its specific target signaling protein/s before it is removed by abundant thiol peroxidases, the 2-Cys peroxiredoxins. This project aims to address this question by utilising a chemogenetic approach in the model yeast Schizosaccharomyces pombe to analyse the effects of producing different levels of H2O2 in specific cell locations. It is expected this approach will provide a better understanding of the spatial control of intracellular redox signalling.

过氧化氢(H_2O_2)等活性氧物种(ROS)具有多种生物来源，是氧代谢的副产物。ROS造成的损害与包括癌症在内的各种与年龄相关的疾病有关。因此，过氧化氢也被用作信号分子，通过促进靶信号蛋白中特定半胱氨酸的氧化来上调ROS防御。我们对这些信号机制的理解在很大程度上是基于对酵母的研究，这些研究涉及向细胞中添加过氧化氢。因此，在被丰富的硫醇过氧化物酶，即2-半胱氨酸过氧化物酶清除之前，还不清楚过氧化氢是如何到达其特定的靶信号蛋白/S并与其反应的。该项目旨在通过在模式酵母裂殖酵母中使用化学发生方法来解决这个问题，以分析在特定细胞位置产生不同水平的过氧化氢的影响。这一方法有望更好地理解细胞内氧化还原信号的空间调控。