Liquid–liquid phase separation in diseases

IF 10.7 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
MedComm Pub Date : 2024-07-13 DOI:10.1002/mco2.640
Xinyue Zhang, Lin Yuan, Wanlu Zhang, Yi Zhang, Qun Wu, Chunting Li, Min Wu, Yongye Huang
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引用次数: 0

Abstract

Liquid–liquid phase separation (LLPS), an emerging biophysical phenomenon, can sequester molecules to implement physiological and pathological functions. LLPS implements the assembly of numerous membraneless chambers, including stress granules and P-bodies, containing RNA and protein. RNA–RNA and RNA–protein interactions play a critical role in LLPS. Scaffolding proteins, through multivalent interactions and external factors, support protein–RNA interaction networks to form condensates involved in a variety of diseases, particularly neurodegenerative diseases and cancer. Modulating LLPS phenomenon in multiple pathogenic proteins for the treatment of neurodegenerative diseases and cancer could present a promising direction, though recent advances in this area are limited. Here, we summarize in detail the complexity of LLPS in constructing signaling pathways and highlight the role of LLPS in neurodegenerative diseases and cancers. We also explore RNA modifications on LLPS to alter diseases progression because these modifications can influence LLPS of certain proteins or the formation of stress granules, and discuss the possibility of proper manipulation of LLPS process to restore cellular homeostasis or develop therapeutic drugs for the eradication of diseases. This review attempts to discuss potential therapeutic opportunities by elaborating on the connection between LLPS, RNA modification, and their roles in diseases.

Abstract Image

疾病中的液-液相分离
液-液相分离(LLPS)是一种新兴的生物物理现象,它可以封存分子以实现生理和病理功能。液-液相分离实现了许多无膜室的组装,包括应激颗粒和P-体,其中含有RNA和蛋白质。RNA-RNA 和 RNA 蛋白相互作用在 LLPS 中发挥着关键作用。支架蛋白通过多价相互作用和外部因素,支持蛋白质-RNA相互作用网络,形成涉及多种疾病(尤其是神经退行性疾病和癌症)的凝聚体。调节多种致病蛋白中的 LLPS 现象以治疗神经退行性疾病和癌症可能是一个很有前景的方向,尽管这一领域的最新进展有限。在此,我们详细总结了 LLPS 在构建信号通路中的复杂性,并强调了 LLPS 在神经退行性疾病和癌症中的作用。我们还探讨了 LLPS 上的 RNA 修饰改变疾病进展的问题,因为这些修饰可影响某些蛋白质的 LLPS 或应激颗粒的形成,并讨论了适当操纵 LLPS 过程以恢复细胞稳态或开发根除疾病的治疗药物的可能性。本综述试图通过阐述 LLPS、RNA 修饰及其在疾病中的作用之间的联系来讨论潜在的治疗机会。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
6.70
自引率
0.00%
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0
审稿时长
10 weeks
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