Abstract：
TDP-43 is an abundant and ubiquitously expressed nuclear protein that becomes dysfunctional in a spectrum of neurodegenerative diseases. TDP-43\'s ability to phase separate and form/enter biomolecular condensates of varying size and composition is critical for its functionality. Despite the high density of phase-separated assemblies in the nucleus and the nuclear abundance of TDP-43, our understanding of the condensate-TDP-43 relationship in this cellular compartment is only emerging. Recent studies have also suggested that misregulation of nuclear TDP-43 condensation is an early event in the neurodegenerative disease amyotrophic lateral sclerosis. This review aims to draw attention to the nuclear facet of functional and aberrant TDP-43 condensation. We will summarise the current knowledge on how TDP-43 containing nuclear condensates form and function and how their homeostasis is affected in disease.
摘要：
TDP-43是一种丰富且普遍表达的核蛋白，在一系列神经退行性疾病中功能失调。TDP-43相分离和形成/进入不同大小和组成的生物分子缩合物的能力对其功能至关重要。尽管原子核中相分离的组件密度很高，并且TDP-43的核丰度很高，但我们对该细胞区室中缩合物-TDP-43关系的理解才刚刚出现。最近的研究还表明，核TDP-43缩合的失调是神经退行性疾病肌萎缩性侧索硬化症的早期事件。这篇综述旨在提请注意功能性和异常TDP-43缩合的核方面。我们将总结有关含TDP-43的核缩合物如何形成和功能以及它们的稳态在疾病中如何受到影响的当前知识。
