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探索热休克蛋白60在阿尔茨海默病和2型糖尿病中的作用:共同药物靶点的建议

Exploring the Role of Hsp60 in Alzheimer's Disease and Type 2 Diabetes: Suggestion for Common Drug Targeting.

作者信息

Zimbone Stefania, Di Rosa Maria Carmela, Chiechio Santina, Giuffrida Maria Laura

机构信息

Institute of Crystallography, National Research Council (CNR-IC), 95126 Catania, Italy.

Cogentech Società Benefit srl Actual Position, 95121 Catania, Italy.

出版信息

Int J Mol Sci. 2023 Aug 5;24(15):12456. doi: 10.3390/ijms241512456.

Abstract

Heat shock protein 60 (Hsp60) is a member of the chaperonin family of heat shock proteins (HSPs), primarily found in the mitochondrial matrix. As a molecular chaperone, Hsp60 plays an essential role in mediating protein folding and assembly, and together with the co-chaperon Hsp10, it is thought to maintain protein homeostasis. Recently, it has been found to localize in non-canonical, extra-mitochondrial sites such as cell membranes or extracellular fluids, particularly in pathological conditions. Starting from its biological function, this review aims to provide a comprehensive understanding of the potential involvement of Hsp60 in Alzheimer's disease (AD) and Type II Diabetes Mellitus (T2DM), which are known to share impaired key pathways and molecular dysfunctions. Fragmentary data reported in the literature reveal interesting links between the altered expression level or localization of this chaperonin and several disease conditions. The present work offers an overview of the past and more recent knowledge about Hsp60 and its role in the most important cellular processes to shed light on neuronal Hsp60 as a potential common target for both pathologies. The absence of any effective cure for AD patients makes the identification of a new molecular target a promising path by which to move forward in the development of new drugs and/or repositioning of therapies already used for T2DM.

摘要

热休克蛋白60(Hsp60)是热休克蛋白(HSPs)伴侣蛋白家族的成员,主要存在于线粒体基质中。作为一种分子伴侣,Hsp60在介导蛋白质折叠和组装中起重要作用,并且与伴侣蛋白Hsp10一起,被认为可维持蛋白质稳态。最近,人们发现它定位于非典型的线粒体外部位点,如细胞膜或细胞外液中,尤其是在病理条件下。从其生物学功能出发,本综述旨在全面了解Hsp60在阿尔茨海默病(AD)和2型糖尿病(T2DM)中的潜在作用,已知这两种疾病存在关键途径受损和分子功能障碍。文献中报道的零散数据揭示了这种伴侣蛋白表达水平或定位的改变与几种疾病状况之间的有趣联系。本研究概述了关于Hsp60的过去和最新知识及其在最重要的细胞过程中的作用,以阐明神经元Hsp60作为这两种疾病潜在共同靶点的情况。由于AD患者缺乏任何有效的治疗方法,确定一个新的分子靶点是在开发新药和/或重新定位已用于T2DM的疗法方面取得进展的一条有前景的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21d3/10419248/b009a110def2/ijms-24-12456-g001.jpg

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