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SIRT3:肝纤维化的潜在治疗靶点。

SIRT3: A potential therapeutic target for liver fibrosis.

机构信息

School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China.

School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Pharmacol Ther. 2024 May;257:108639. doi: 10.1016/j.pharmthera.2024.108639. Epub 2024 Mar 30.

Abstract

Sirtuin3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase located in the mitochondria, which mainly regulates the acetylation of mitochondrial proteins. In addition, SIRT3 is involved in critical biological processes, including oxidative stress, inflammation, DNA damage, and apoptosis, all of which are closely related to the progression of liver disease. Liver fibrosis characterized by the deposition of extracellular matrix is a result of long termed or repeated liver damage, frequently accompanied by damaged hepatocytes, the recruitment of inflammatory cells, and the activation of hepatic stellate cells. Based on the functions and pharmacology of SIRT3, we will review its roles in liver fibrosis from three aspects: First, the main functions and pharmacological effects of SIRT3 were investigated based on its structure. Second, the roles of SIRT3 in major cells in the liver were summarized to reveal its mechanism in developing liver fibrosis. Last, drugs that regulate SIRT3 to prevent and treat liver fibrosis were discussed. In conclusion, exploring the pharmacological effects of SIRT3, especially in the liver, may be a potential strategy for treating liver fibrosis.

摘要

Sirtuin3(SIRT3)是一种位于线粒体中的烟酰胺腺嘌呤二核苷酸(NAD)依赖性蛋白去乙酰化酶,主要调节线粒体蛋白的乙酰化。此外,SIRT3 还参与了关键的生物学过程,包括氧化应激、炎症、DNA 损伤和细胞凋亡,所有这些都与肝病的进展密切相关。以细胞外基质沉积为特征的肝纤维化是长期或反复肝损伤的结果,常伴有受损的肝细胞、炎症细胞的募集和肝星状细胞的激活。基于 SIRT3 的功能和药理学特性,我们将从三个方面综述其在肝纤维化中的作用:首先,基于 SIRT3 的结构研究了其主要功能和药理学作用。其次,总结了 SIRT3 在肝脏主要细胞中的作用,以揭示其在肝纤维化发生中的机制。最后,讨论了调节 SIRT3 以预防和治疗肝纤维化的药物。总之,探索 SIRT3 的药理学作用,特别是在肝脏中的作用,可能是治疗肝纤维化的一种潜在策略。

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