聚集体自噬研究进展

Recent advances in aggrephagy research

错误折叠蛋白在细胞内大量堆积后会形成蛋白聚集体,干扰细胞正常生理活动,以至引发各种人类疾病,尤其是神经退行性疾病。因此,研究聚集体的形成和清除过程对治疗神经退行性疾病具有重要意义。蛋白聚集体在形成过程中会受到相分离的调控,在液相、固相等多种状态间转变,这影响了聚集体的性质及其清除方式。尽管细胞内多种蛋白质量监测系统均可参与错误折叠蛋白的清除,但是一旦聚集体形成,通常需要通过自噬途径清除,即聚集体自噬过程。在聚集体自噬中,p62、NBR1、TAX1BP1、Tollip、CCT2等自噬受体能够帮助自噬系统识别蛋白聚集体,在聚集体的清除中发挥重要作用。文章主要介绍聚集体的形成以及通过自噬清除的过程,并聚焦于聚集体自噬领域的最新研究进展。

Misfolded proteins accumulate in cells to form protein aggregates, which interfere with the normal physiological activities of cells and cause various human diseases, especially neurodegenerative diseases. Therefore, studying the process of aggregate formation and clearance is significant for the therapy of neurodegenerative diseases. Protein aggregates are regulated by phase separation during their formation, transitioning from liquid to solid states, which affects the properties and removal of aggregates.Although a variety of intracellular protein quality control systems can be involved in the removal of misfolded proteins, protein aggregates need to be cleared through the autophagy pathway, and the process is called aggrephagy. In aggrephagy, autophagy receptors such as p62, NBR1, TAX1BP1, Tollip, and CCT2 can help the autophagy system to recognize protein aggregates, which plays an important role in the removal of aggregates. This article will introduce the formation and autophagic clearance of aggregates,with a focus on the latest research progress in the field of aggrephagy.