非酒精性脂肪肝病 (NAFLD) 是一种以脂肪堆积为特征但不过度饮酒的肝脏疾病，是一个重大的全球健康负担。 NAFLD 发病机制背后复杂的分子格局涉及脂质处理、炎症、氧化应激和线粒体功能障碍，其中内质网 (ER) 应激成为关键因素。 ER 应激触发未折叠蛋白反应 (UPR)，影响 NAFLD 中的肝脂肪变性，并导致炎症、纤维化和 NASH 进展，最终发展为肝细胞癌 (HCC)。热休克蛋白 (HSP)，包括 HSP20 和 HSP27、HSP60、HSP70、GRP78 和 HSP90 等小 HSP，是细胞应激反应不可或缺的一部分。它们有助于蛋白质折叠、防止聚集并促进降解，从而减轻应激条件下的细胞损伤。在 NAFLD 中，异常的 HSP 表达和功能有助于疾病发病机制。了解 HSP 亚型在 NAFLD 中的具体作用可以为潜在的治疗干预提供见解。这篇综述讨论了 HSP 在 NAFLD 病理生理学中的参与，并强调了它们的治疗潜力。通过阐明 NAFLD 中 HSP 介导的保护作用的分子机制，本文旨在为这种常见肝脏疾病的靶向治疗的开发铺平道路。© 2024。作者。

Non-alcoholic fatty liver disease (NAFLD), a spectrum of liver conditions characterized by fat accumulation without excessive alcohol consumption, represents a significant global health burden. The intricate molecular landscape underlying NAFLD pathogenesis involves lipid handling, inflammation, oxidative stress, and mitochondrial dysfunction, with endoplasmic reticulum (ER) stress emerging as a key contributor. ER stress triggers the unfolded protein response (UPR), impacting hepatic steatosis in NAFLD and contributing to inflammation, fibrosis, and progression to NASH and eventually hepatocellular carcinoma (HCC). Heat shock proteins (HSPs), including small HSPs such as HSP20 and HSP27, HSP60, HSP70, GRP78, and HSP90, are integral to cellular stress responses. They aid in protein folding, prevent aggregation, and facilitate degradation, thus mitigating cellular damage under stress conditions. In NAFLD, aberrant HSP expression and function contribute to disease pathogenesis. Understanding the specific roles of HSP subtypes in NAFLD offers insights into potential therapeutic interventions. This review discusses the involvement of HSPs in NAFLD pathophysiology and highlights their therapeutic potential. By elucidating the molecular mechanisms underlying HSP-mediated protection in NAFLD, this article aims to pave the way for the development of targeted therapies for this prevalent liver disorder.© 2024. The Author(s).