Ferroptosis as an emerging target in rheumatoid arthritis

Front Immunol. 2023 Oct 19:14:1260839. doi: 10.3389/fimmu.2023.1260839. eCollection 2023.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. Due to the rise in the incidence rate of RA and the limitations of existing therapies, the search for new treatment strategies for RA has become a global focus. Ferroptosis is a novel programmed cell death characterized by iron-dependent lipid peroxidation, with distinct differences from apoptosis, autophagy, and necrosis. Under the conditions of iron accumulation and the glutathione peroxidase 4 (GPX4) activity loss, the lethal accumulation of lipid peroxide is the direct cause of ferroptosis. Ferroptosis mediates inflammation, oxidative stress, and lipid oxidative damage processes, and also participates in the occurrence and pathological progression of inflammatory joint diseases including RA. This review provides insight into the role and mechanism of ferroptosis in RA and discusses the potential and challenges of ferroptosis as a new therapeutic strategy for RA, with an effort to provide new targets for RA prevention and treatment.

Keywords: emerging target; ferroptosis; iron metabolism; lipid peroxidation; rheumatoid arthritis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Arthritis, Rheumatoid* / drug therapy
  • Ferroptosis*
  • Humans
  • Iron / metabolism
  • Lipid Peroxidation

Substances

  • Iron

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the National Natural Science Foundation of China (No 81403484); Anhui Province University Natural Science Fund Project of China (No KJ2019A0448); National Project Cultivation Fund Project Plan (No. 2019py01) Anhui Province Clinical Medical Research Center [Anhui Provincial Science and Technology Department Anhui Social Science (2020) No. 41]; Anhui Province Traditional Chinese Medicine Inheritance Innovation Scientific Research Project (No 2020ccyb13); The training Program of Outstanding talents in Colleges and Universities (No. gxgnfx2021122); Anhui Province Medical and Health Key Specialist Construction Project (Anhui Health Letter [2021] No.273).