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热休克蛋白 60 作为药物靶点。

HSP60 as a drug target.

机构信息

Department of Chemistry, Faculty of Science, Gakushuin University, Japan.

出版信息

Curr Pharm Des. 2013;19(3):441-51.

Abstract

Heat shock proteins (HSPs) are ubiquitous and evolutionary conserved proteins induced by cell stress. HSP60, in particular, is a typical mitochondrial molecular chaperone that is known to assist nascent polypeptides to reach a native conformation. HSP60 is also known to interact with HSP10. In the last decade, HSP60 has been detected in the cytosol, the cell surface, the extracellular space, and biological fluids. HSP60 elicits potent proinflammatory response in cells of the innate immune system and serves as a danger signal of stressed or damaged cells. As cytosolic HSP60 levels gradually increase or decrease during carcinogenesis in various organs, HSP60 can be used as a biomarker for the diagnosis and prognosis of preneoplastic and neoplastic lesions. In this review, we summarize recent discoveries on the important roles of HSP60 in various diseases ranging from autoimmune diseases to tumors. Furthermore, small molecules targeting HSP60, which were the target of intensive investigations in the last few years, are also summarized. The possibility of utilizing HSP60 as a new drug target for the treatment of certain diseases is examined.

摘要

热休克蛋白(HSPs)是细胞应激诱导的普遍存在且进化上保守的蛋白质。HSP60 是一种典型的线粒体分子伴侣,已知其可帮助新生多肽达到天然构象。HSP60 还与 HSP10 相互作用。在过去的十年中,HSP60 已在细胞质、细胞表面、细胞外空间和生物液中被检测到。HSP60 可引发固有免疫系统细胞的强烈炎症反应,并作为应激或受损细胞的危险信号。在各种器官的癌变过程中,细胞质 HSP60 水平逐渐增加或减少,HSP60 可作为癌前和肿瘤病变的诊断和预后的生物标志物。在这篇综述中,我们总结了 HSP60 在从自身免疫性疾病到肿瘤等各种疾病中的重要作用的最新发现。此外,还总结了近年来 HSP60 作为一个新的药物靶点的小分子靶向治疗的研究进展。还探讨了利用 HSP60 作为治疗某些疾病的新药物靶点的可能性。

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