Abstract
在多种逆境条件下,真核生物通常会在细胞质中形成呈聚集状颗粒的mRNA-蛋白质复合体,即应激颗粒(stress granules, SGs)。SGs的形成具有重要生理意义,包括通过调控mRNA翻译以及抑制细胞凋亡相关信号通路等机制,将逆境压力对细胞造成的损伤最小化,并促进细胞对逆境条件的适应以及在逆境条件下的存活。研究表明,SGs与多种疾病的发生关联紧密,包括多种类型的肿瘤、神经退行性疾病以及病毒感染相关疾病等。肿瘤细胞利用SGs促进了逆境条件下的存活,而一些神经退行性疾病中蛋白聚集体的形成也与异常SGs密切相关。因此,SGs逐渐成为以上疾病的新型药物靶点并受到越来越多研究的关注,SGs抑制剂也就应运而生。本文主要就靶向SGs的化合物及其在相关疾病中的应用进行了总结和探讨,以期为SGs抑制剂的研究及其临床应用提供参考。 Upon a variety of adverse conditions, eukaryotic cells usually form aggregating droplet-like mRNA-protein complexes namely stress granules (SGs) in the cytoplasm. The physiological signifi-cance of SGs formation is to minimize stress-related damage, promote stress adaptation and cell survival via regulation of mRNA translation and inhibition of apoptosis-related signaling pathways. Accordingly, dysregulation of SGs are closely associated with many diseases, including many types of cancer, neurodegenerative diseases and viral infectious diseases SGs hijacked by cancer cells promote the survival of cancer cells under adverse conditions, while protein aggregates found in some neurodegenerative diseases are also related to abnormal SGs. Therefore, SGs attract the at-tention of growing studies as a new therapeutic target, concomitantly with the emergence of SGs in-hibitors. This review will summarize and discuss recent progress on compounds targeting SGs and their application in SGs-related diseases, which may be helpful for research and therapeutic appli-cation of SGs inhibitors.