Structural determinants of amyloid strain heterogeneity in distinct phenotypes of Alzheimer's disease

阿尔茨海默病不同表型中淀粉样蛋白菌株异质性的结构决定因素

• 批准号: 10375763
• 负责人: Christopher P Jaroniec
• 金额: $ 40.07万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10375763
• 关键词: Administrative Supplement; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid; Amyloid beta-Protein; Area; Award; Brain; Brain Pathology; Cell Death; Deposition; Development; Disease; Environment; Foundations; Frontotemporal Dementia; Future; Goals; Heterogeneity; Lead; Liquid substance; Neurodegenerative Disorders; Parents; Pathogenicity; Pathologic; Phase; Phenotype; Physical condensation; Process; Property; Proteins; Research; Role; Structure; hyperphosphorylated tau; insight; novel therapeutic intervention; tau Proteins; tau aggregation

The deposition of aggregated hyperphosphorylated tau protein in brain is directly associated with cell death and propagation of brain pathology in Alzheimer's disease and several other neurodegenerative diseases, including frontotemporal dementia. The major goal of the parent award RF1 AG 061797 is to elucidate the relationship between structural properties of tau and Aβ aggregates and phenotypic variability of Alzheimer's disease and related disorders. An important recent development is the finding that, akin to some other proteins involved in neurodegenerative diseases, tau can undergo liquid-liquid phase separation, forming condensates in which protein concentration is extremely high. The environment of these condensates may have a major impact on the aggregation properies of tau, contributing to the pathogenic process. The purpose of this Administrative Supplement is to expand the scope of studies in the parent award into this rapidly emerging area of research, with the main specific objective to elucidate the mechanisms of tau liquid-liquid phase separation and the role of different types of interactions in this process. The insights gained in this research should provide a necessary foundation for future studies aimed at understanding the intricate role of liquid-liquid phase separation in pathological aggregation of tau in Alzheimer's disease and related disorders.

总磷酸化tau蛋白在脑中的沉积与细胞死亡直接相关 阿尔茨海默氏病和其他几种神经退行性疾病的传播，包括 额颞痴呆。父母奖RF1 AG 061797的主要目标是阐明这种关系 在tau和Aβ聚集体的结构特性与阿尔茨海默氏病的表型变异性之间 相关疾病。最近的一个重要发展是，类似于其他涉及的其他蛋白质的发现 神经退行性疾病，tau可以进行液态液相分离，形成冷凝水，其中 蛋白质浓度极高。这些冷凝水的环境可能对 tau的聚集特性，导致致病过程。此行政的目的 补充是将父母奖中的研究范围扩展到这个快速新兴的研究领域， 具有阐明tau液体液相分离机理的主要特定目标以及 在此过程中，不同类型的互动。这项研究中获得的见解应提供必要的 未来研究的基础旨在理解液 - 液相分离的复杂作用 阿尔茨海默氏病和相关疾病中tau的病理聚集。