Targeting ferroptosis, a novel programmed cell death, for the potential of alcohol-related liver disease therapy

Jing-Fen Shi; Yu'e Liu; Yan Wang; Ru Gao; Yi Wang; Jun Liu

doi:10.3389/fphar.2023.1194343

Targeting ferroptosis, a novel programmed cell death, for the potential of alcohol-related liver disease therapy

Front Pharmacol. 2023 May 5:14:1194343. doi: 10.3389/fphar.2023.1194343. eCollection 2023.

Authors

Jing-Fen Shi^{1

2}, Yu'e Liu³, Yan Wang², Ru Gao², Yi Wang⁴, Jun Liu^{2

5}

Affiliations

¹ Institute for Health Policy and Hospital Management, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
² Wenjiang District People's Hospital of Chengdu, Chengdu, China.
³ Tongji University Cancer Center, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Tongji University, Shanghai, China.
⁴ Department of Critical Care Medicine, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
⁵ Department of Ultrasound Medicine, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

Abstract

Ferroptosis is a new iron-dependent cell death mode, which is different from the other types of programmed cell death, such as apoptosis, necrosis, and autophagy. Ferroptosis is characterized by a process in which fatal lipids from lipid peroxidation accumulate in cells and eventually lead to cell death. Alcohol-related liver disease (ALD) is a type of liver injury caused by excessive alcohol intake. Alcohol-related liver disease is a broad-spectrum disease category, which includes fatty liver, steatohepatitis, hepatitis, cirrhosis, and hepatocellular tumors. Recent studies have found that ferroptosis is involved in the pathological development of non-viral liver diseases. Therefore, ferroptosis may be an ideal target for the treatment of non-viral liver diseases. In this review article, we will elaborate the molecular mechanism and regulatory mechanism of ferroptosis, explore the key role of ferroptosis in the Alcohol-related liver disease process, and summarize the existing targeted ferroptosis drugs and their feasibility for the treatment of Alcohol-related liver disease.

Keywords: ALD; GPx4; ROS; ferroptosis; ferroptosis inducers; ferroptosis inhibitors; p53.

Publication types

Review

Grants and funding

This research was supported by the National Natural Science Foundation of China (81802504), Sichuan Science and Technology Bureau (2022YFH0005 and 2023YFH0010), the Science and Technology Innovation Project of Chengdu, China (No. 2021-YF05-00225-SN), a Sichuan Medical Association grant (No. Q19037).