Cellular Stress

细胞压力

• 批准号: CRC-2021-00117
• 负责人: Audas, Timothy
• 金额: $ 7.29万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Canada Research Chairs
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761176
• 关键词: Cellular; Stress

Neurological disorders (e.g, Alzheimer's, Parkinson's and related dementias) affect over 500,000 Canadians and cost the healthcare system ~$10 billion per year, representing a significant emotional and economic drain on the entire Canadian population. These diseases are caused by abnormal and toxic protein clumping in the brains of affected individuals, leading to memory loss, confusion, and impaired motor function. How and why these aggregates form is an important question that may provide insights into prevention and treatment. Scientists are struggling to find genes or environmental factors associated with the development of these neurological disorders. Dr. Timothy Audas studies a natural, reversible counterpart to these toxic clumps, where nearly identical protein aggregates form rapidly and disassemble in response to specific environmental signals. His team is using cultured mammalian cells and model organisms (e.g. fruit flies and yeast) to understand how this basic biological pathway works. Their goal is to: (1) determine which proteins aggregate under specific conditions, (2) decipher how these natural protein clumps help cells survive harsh stress treatments, and (3) identify molecules and drugs that can control this aggregation process. By learning more about this cellular pathway Dr. Audas' team will enhance our understanding of cell adaptability, and potentially generate pharmaceutical avenues for the development of therapeutic remedies to treat those afflicted with debilitating neurological disorders.

神经系统疾病（如阿尔茨海默氏症、帕金森氏症和相关的痴呆症）影响了50多万加拿大人，每年给医疗保健系统造成约100亿美元的损失，对整个加拿大人口造成了重大的情感和经济损失。这些疾病是由患者大脑中异常和有毒的蛋白质聚集引起的，导致记忆丧失、思维混乱和运动功能受损。这些聚集体如何以及为什么形成是一个重要的问题，可能为预防和治疗提供见解。科学家们正在努力寻找与这些神经系统疾病发展相关的基因或环境因素。蒂莫西·奥达斯博士研究了一种天然的、可逆的与这些有毒团块相对应的物质，在这种物质中，几乎相同的蛋白质聚集体迅速形成，并在特定的环境信号下分解。他的团队正在使用培养的哺乳动物细胞和模式生物（如果蝇和酵母）来了解这种基本的生物途径是如何工作的。他们的目标是：(1)确定哪些蛋白质在特定条件下聚集；(2)破译这些天然蛋白质团块如何帮助细胞在严酷的应激处理中生存；(3)识别可以控制这种聚集过程的分子和药物。通过对这种细胞途径的更多了解，Audas博士的团队将增强我们对细胞适应性的理解，并有可能为开发治疗性药物提供途径，以治疗那些患有衰弱性神经系统疾病的人。