细胞内的代谢反应发生在有或没有边界的各种隔离隔室中。后者被称为无膜细胞器(MLO)。MLO显示出类似液体的性质并且通过称为液-液相分离(LLPS)的方法形成。MLO有助于不同的分子相互作用,如蛋白质-蛋白质,蛋白质-RNA,和由各种因素驱动的RNA-RNA,例如内在障碍的多价。MLO参与几种细胞信号传导途径,如转录,免疫反应,和细胞组织。然而,在不同的病理中发现了这些过程的破坏。最近,已经证明蛋白质聚集,一些神经退行性疾病的特征,进行类似的相分离。Tau蛋白是阿尔茨海默病(AD)的主要神经原纤维缠结成分。这种蛋白质可以在体外和体内进行相分离以形成被称为tau液滴的MLO,这个过程可以通过几个因素来促进,包括拥挤剂,RNA,和磷酸化。Tau液滴已显示成熟为不溶性聚集体,表明该过程可能先于并诱导AD的神经变性。在这里,我们回顾了细胞内液滴形成的主要因素。此外,我们重点介绍了有关AD中相分离后tau聚集的最新发现,以及在此过程中可以针对这种病理的进展探索的潜在治疗策略。
Metabolic reactions within cells occur in various isolated compartments with or without borders, the latter being known as membrane-less organelles (MLOs). The MLOs show liquid-like properties and are formed by a process known as liquid-liquid phase separation (LLPS). MLOs contribute to different molecules interactions such as protein-protein, protein-RNA, and RNA-RNA driven by various factors, such as multivalency of intrinsic disorders. MLOs are involved in several cell signaling pathways such as transcription, immune response, and cellular organization. However, disruption of these processes has been found in different pathologies. Recently, it has been demonstrated that protein aggregates, a characteristic of some neurodegenerative diseases, undergo similar phase separation. Tau protein is known as a major neurofibrillary tangles component in Alzheimer\'s disease (AD). This protein can undergo phase separation to form a MLO known as tau droplet in vitro and in vivo, and this process can be facilitated by several factors, including crowding agents, RNA, and phosphorylation. Tau droplet has been shown to mature into insoluble aggregates suggesting that this process may precede and induce neurodegeneration in AD. Here we review major factors involved in liquid droplet formation within a cell. Additionally, we highlight recent findings concerning tau aggregation following phase separation in AD, along with the potential therapeutic strategies that could be explored in this process against the progression of this pathology.