FUS 和 TDP-43 在健康与疾病中的相态。
FUS and TDP-43 Phases in Health and Disease.
机构信息
Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
Trends Biochem Sci. 2021 Jul;46(7):550-563. doi: 10.1016/j.tibs.2020.12.005. Epub 2021 Jan 11.
Abstract
The distinct prion-like domains (PrLDs) of FUS and TDP-43, modulate phase transitions that result in condensates with a range of material states. These assemblies are implicated in both health and disease. In this review, we examine how sequence, structure, post-translational modifications, and RNA can affect the self-assembly of these RNA-binding proteins (RBPs). We discuss how our emerging understanding of FUS and TDP-43 liquid-liquid phase separation (LLPS) and aggregation, could be leveraged to design new therapies for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and limbic-predominant age-related TDP-43 encephalopathy (LATE).
摘要
FUS 和 TDP-43 的独特类朊病毒结构域（PrLDs）调节相转变，导致具有多种物质状态的凝聚物。这些组装体与健康和疾病都有关联。在这篇综述中，我们研究了序列、结构、翻译后修饰和 RNA 如何影响这些 RNA 结合蛋白（RBPs）的自组装。我们讨论了我们对 FUS 和 TDP-43 液-液相分离（LLPS）和聚集的理解如何被利用来设计治疗肌萎缩侧索硬化症（ALS）、额颞叶痴呆（FTD）和边缘为主的与年龄相关的 TDP-43 脑病（LATE）等神经退行性疾病的新疗法。
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