Milicevic Katarina, Rankovic Branislava, Andjus Pavle R, Bataveljic Danijela, Milovanovic Dragomir
Center for Laser Microscopy, Faculty of Biology, Institute of Physiology and Biochemistry "Ivan Djaja", University of Belgrade, Belgrade, Serbia.
Laboratory of Molecular Neuroscience, German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Front Cell Dev Biol. 2022 Feb 17;10:840256. doi: 10.3389/fcell.2022.840256. eCollection 2022.
Liquid-liquid phase separation (LLPS) is emerging as a major principle for the mesoscale organization of proteins, RNAs, and membrane-bound organelles into biomolecular condensates. These condensates allow for rapid cellular responses to changes in metabolic activities and signaling. Nowhere is this regulation more important than in neurons and glia, where cellular physiology occurs simultaneously on a range of time- and length-scales. In a number of neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS), misregulation of biomolecular condensates leads to the formation of insoluble aggregates-a pathological hallmark of both sporadic and familial ALS. Here, we summarize how the emerging knowledge about the LLPS of ALS-related proteins corroborates with their aggregation. Understanding the mechanisms that lead to protein aggregation in ALS and how cells respond to these aggregates promises to open new directions for drug development.
液-液相分离（LLPS）正成为蛋白质、RNA和膜结合细胞器在中尺度上组织形成生物分子凝聚物的主要原理。这些凝聚物使细胞能够对代谢活动和信号变化做出快速反应。这种调节在神经元和胶质细胞中最为重要，因为细胞生理活动在一系列时间和长度尺度上同时发生。在许多神经退行性疾病中，如肌萎缩侧索硬化症（ALS），生物分子凝聚物的调节异常会导致不溶性聚集体的形成——这是散发性和家族性ALS的病理标志。在这里，我们总结了关于ALS相关蛋白质的液-液相分离的新知识如何与它们的聚集相互印证。了解导致ALS中蛋白质聚集的机制以及细胞如何对这些聚集体做出反应，有望为药物开发开辟新的方向。
