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非酒精性肝病中的铁死亡:分子机制与治疗意义

Ferroptosis in non-alcoholic liver disease: Molecular mechanisms and therapeutic implications.

作者信息

Cheng Zilu, Chu Huikuan, Zhu Qingjing, Yang Ling

机构信息

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Jinyintan Hospital, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Nutr. 2023 Mar 13;10:1090338. doi: 10.3389/fnut.2023.1090338. eCollection 2023.


DOI:10.3389/fnut.2023.1090338
PMID:36992907
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10040549/
Abstract

Ferroptosis refers to a novel modality of regulated cell death characterized by excessive iron accumulation and overwhelming lipid peroxidation, which takes an important part in multiple pathological processes associated with cell death. Considering the crucial roles of the liver in iron and lipid metabolism and its predisposition to oxidative insults, more and more studies have been conducted to explore the relationship between ferroptosis and various liver disorders, including non-alcoholic fatty liver disease (NAFLD). With increased morbidity and high mortality rates, NAFLD has currently emerged as a global public health issue. However, the etiology of NAFLD is not fully understood. In recent years, an accumulating body of evidence have suggested that ferroptosis plays a pivotal role in the pathogenesis of NAFLD, but the precise mechanisms underlying how ferroptosis affects NAFLD still remain obscure. Here, we summarize the molecular mechanisms of ferroptosis and its complicated regulation systems, delineate the different effects that ferroptosis exerts in different stages of NAFLD, and discuss some potential effective therapies targeting ferroptosis for NAFLD treatment, which putatively points out a novel direction for NAFLD treatment.

摘要

铁死亡是一种新型的程序性细胞死亡方式,其特征是铁过量积累和脂质过氧化反应失控,在与细胞死亡相关的多种病理过程中起重要作用。鉴于肝脏在铁和脂质代谢中的关键作用及其易受氧化损伤的特性,越来越多的研究致力于探索铁死亡与包括非酒精性脂肪性肝病(NAFLD)在内的各种肝脏疾病之间的关系。随着发病率和死亡率的上升,NAFLD目前已成为一个全球性的公共卫生问题。然而,NAFLD的病因尚未完全明确。近年来,越来越多的证据表明铁死亡在NAFLD的发病机制中起关键作用,但铁死亡如何影响NAFLD的具体机制仍不清楚。在此,我们总结了铁死亡的分子机制及其复杂的调控系统,阐述了铁死亡在NAFLD不同阶段所发挥的不同作用,并讨论了一些针对铁死亡的潜在有效治疗方法用于NAFLD的治疗,这可能为NAFLD的治疗指出一个新的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c2/10040549/56b7c6cfacbd/fnut-10-1090338-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c2/10040549/e024b91803f8/fnut-10-1090338-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c2/10040549/56b7c6cfacbd/fnut-10-1090338-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c2/10040549/e024b91803f8/fnut-10-1090338-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c2/10040549/56b7c6cfacbd/fnut-10-1090338-g002.jpg

相似文献

[1]
Ferroptosis in non-alcoholic liver disease: Molecular mechanisms and therapeutic implications.

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[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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[8]
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[10]
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本文引用的文献

[1]
Iron Status and NAFLD among European Populations: A Bidirectional Two-Sample Mendelian Randomization Study.

Nutrients. 2022-12-8

[2]
Attenuation by Time-Restricted Feeding of High-Fat and High-Fructose Diet-Induced NASH in Mice Is Related to Per2 and Ferroptosis.

Oxid Med Cell Longev. 2022

[3]
Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH).

Signal Transduct Target Ther. 2022-8-13

[4]
Iron Absorption: Factors, Limitations, and Improvement Methods.

ACS Omega. 2022-6-10

[5]
Ferroptosis in Chronic Liver Diseases: Opportunities and Challenges.

Front Mol Biosci. 2022-6-3

[6]
Targeting Mitochondrial ROS-Mediated Ferroptosis by Quercetin Alleviates High-Fat Diet-Induced Hepatic Lipotoxicity.

Front Pharmacol. 2022-4-12

[7]
Contribution of classification based on ferroptosis-related genes to the heterogeneity of MAFLD.

BMC Gastroenterol. 2022-2-10

[8]
The multifaceted role of ferroptosis in liver disease.

Cell Death Differ. 2022-3

[9]
Ferroptosis and metabolic dysfunction-associated fatty liver disease: Is there a link?

Liver Int. 2022-7

[10]
Role of Ferroptosis in Non-Alcoholic Fatty Liver Disease and Its Implications for Therapeutic Strategies.

Biomedicines. 2021-11-10

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