神经退行性疾病与许多不同的内源性无序蛋白质或含有内源性无序区域的蛋白质的病理性沉积相关。最新的证据表明，这些蛋白质可以发生液液相分离，并在细胞中形成无膜小器官。此外，这些蛋白质形成的生物分子凝结物可能发生液-固相转变，由此成熟为淀粉样纤维、寡聚体物种或无定形聚集体，从而导致几种神经退行性疾病的病理学。在这里，我们讨论了与神经退行有关的神经元蛋白质tau、α-synuclein、sarcoma融合(FUS)以及43kDa的反应DNA结合蛋白(TDP-43)的相分离作用在病理性蛋白质聚集的背景下的作用。版权所有© 2023 Elsevier Ltd. 保留所有权利。

Neurodegenerative diseases are associated with the pathological deposition of many different intrinsically disordered proteins or proteins with intrinsically disordered regions. Recent evidence suggests that these proteins can undergo liquid-liquid phase separation and also form membrane-less organelles in cells. Additionally, the biomolecular condensates formed by these proteins may undergo liquid-to-solid phase transition thereby maturating to amyloid fibrils, oligomeric species, or amorphous aggregates and contributing to the pathology of several neurodegenerative diseases. Here we discuss the role of phase separation of the neuronal proteins tau, α-synuclein, fused in sarcoma (FUS), and the transactive response DNA-binding protein of 43 kDa (TDP-43) that are associated with neurodegeneration in the context of pathological protein aggregation.Copyright © 2023 Elsevier Ltd. All rights reserved.