针对非酒精性脂肪肝的细胞死亡:机制和靶向疗法。

IF 6.1 2区 生物学 Q1 CELL BIOLOGY Cell Death Discovery Pub Date : 2024-09-07 DOI:10.1038/s41420-024-02168-z
Hui-Li Xu, Sheng-Rong Wan, Ying An, Qi Wu, Yi-Hang Xing, Chen-Hao Deng, Ping-Ping Zhang, Yang Long, Bu-Tuo Xu, Zong-Zhe Jiang
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引用次数: 0

摘要

非酒精性脂肪性肝病(NAFLD)是一类慢性肝病,病变范围从单纯性脂肪变性(NAFL)到非酒精性脂肪性肝炎(NASH)不等,以脂质蓄积、炎症激活、纤维化和细胞死亡为特征。迄今为止,针对脂肪酸代谢、炎症因子和肝纤维化的疗法进行了大量临床前研究或临床试验,以开发治疗非酒精性脂肪肝/NASH 的有效药物。然而,尽管在非酒精性脂肪肝/NASH 的整个进展过程中存在各种细胞死亡模式,但针对细胞死亡信号的疗法却寥寥无几。在此,我们总结了非酒精性脂肪肝中细胞死亡的四种类型,包括凋亡、坏死、热凋亡和铁凋亡,以及游离脂肪酸和 LPS 等致病因子在非酒精性脂肪肝发病过程中诱导细胞死亡的潜在分子机制。此外,我们还综述了细胞死亡靶向疗法对非酒精性脂肪肝的影响。总之,我们的综述全面揭示了各种细胞死亡模式在非酒精性脂肪肝进展过程中的作用,希望能为治疗干预开辟新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Targeting cell death in NAFLD: mechanisms and targeted therapies.

Nonalcoholic fatty liver disease (NAFLD) is a group of chronic liver disease which ranges from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) and is characterized by lipid accumulation, inflammation activation, fibrosis, and cell death. To date, a number of preclinical studies or clinical trials associated with therapies targeting fatty acid metabolism, inflammatory factors and liver fibrosis are performed to develop effective drugs for NAFLD/NASH. However, few therapies are cell death signaling-targeted even though the various cell death modes are present throughout the progression of NAFLD/NASH. Here we summarize the four types of cell death including apoptosis, necroptosis, pyroptosis, and ferroptosis in the NAFLD and the underlying molecular mechanisms by which the pathogenic factors such as free fatty acid and LPS induce cell death in the pathogenesis of NAFLD. In addition, we also review the effects of cell death-targeted therapies on NAFLD. In summary, our review provides comprehensive insight into the roles of various cell death modes in the progression of NAFLD, which we hope will open new avenues for therapeutic intervention.

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来源期刊
Cell Death Discovery
Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
8.30
自引率
1.40%
发文量
468
审稿时长
9 weeks
期刊介绍: Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
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