SIRT3:肝纤维化的潜在治疗靶点

IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmacology & Therapeutics Pub Date : 2024-03-30 DOI:10.1016/j.pharmthera.2024.108639
Yan Ning , Xinyue Dou , Zhichao Wang , Kao Shi , Zeping Wang , Chuan Ding , Xianan Sang , Xiang Zhong , Meiyu Shao , Xin Han , Gang Cao
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引用次数: 0

摘要

Sirtuin3(SIRT3)是一种烟酰胺腺嘌呤二核苷酸(NAD+)依赖性蛋白去乙酰化酶,位于线粒体中,主要调节线粒体蛋白的乙酰化。此外,SIRT3 还参与重要的生物过程,包括氧化应激、炎症、DNA 损伤和细胞凋亡,所有这些过程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肝脏长期或反复受损的结果,经常伴随着肝细胞受损、炎症细胞招募和肝星状细胞活化。基于 SIRT3 的功能和药理,我们将从三个方面回顾其在肝纤维化中的作用:首先,根据SIRT3的结构研究其主要功能和药理作用。其次,总结 SIRT3 在肝脏主要细胞中的作用,揭示其在肝纤维化中的作用机制。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的药理作用,尤其是在肝脏中的作用,可能是治疗肝纤维化的一种潜在策略。
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SIRT3: A potential therapeutic target for liver fibrosis

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.

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来源期刊
CiteScore
23.00
自引率
0.70%
发文量
222
审稿时长
90 days
期刊介绍: Pharmacology & Therapeutics, in its 20th year, delivers lucid, critical, and authoritative reviews on current pharmacological topics.Articles, commissioned by the editor, follow specific author instructions.This journal maintains its scientific excellence and ranks among the top 10 most cited journals in pharmacology.
期刊最新文献
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