ROS-Dependent Lipid Peroxidation and Reliant Antioxidant Ferroptosis-Suppressor-Protein 1 in Rheumatoid Arthritis: a Covert Clue for Potential Therapy

Inflammation. 2021 Feb;44(1):35-47. doi: 10.1007/s10753-020-01338-2. Epub 2020 Sep 12.

Abstract

Rheumatoid arthritis (RA) is a common systemic autoimmune disease with a prevalence of about 1% in which genetic and environmental risk factors both participate in performance of disease. Though several studies contributed in identifying its etiology and pathogenesis, the underlying mechanisms are still unknown. To date, so as palliative for RA, cure strategies are still popular. Hypoxia and oxidative stress are implicated to RA development and subsequent ROS-mediated cell death which is a critical feature for RA progression. As for cell death and lipid peroxidation, ferroptosis is a newly discovered, iron-dependent, and non-apoptotic cell death which draws various attention due to its potential strategies for cancer therapy. Meanwhile, ferroptosis-suppressor-protein 1 (FSP1) is recently identified as a seminal breakthrough owing to its property of versus ferroptosis. By virtue of the complicated research progress on FSP1 with ferroptosis, in this review, we summarize the whole region of relevance between ROS and RA. Taken together, we hypothesize that ROS accompanied with ferroptosis may function as a reciprocal with cell death that interplays with RA; besides, FSP1 might become a potential therapeutic target for RA because of its potential interaction with TNF-α/ROS-positive feedback loop. This review systematically concludes the previous understandings about identification of ROS and FSP1 and, in turn, aims to provide references for further achievements of them and hints on elucidation of its thorough underlying mechanisms.

Keywords: FSP1; ROS; TNF-α; cell death; ferroptosis; rheumatoid arthritis.

Publication types

  • Systematic Review

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Apoptosis Regulatory Proteins / metabolism*
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / therapy
  • Ferroptosis / physiology*
  • Humans
  • Lipid Peroxidation / physiology*
  • Mitochondrial Proteins / metabolism*
  • Reactive Oxygen Species / metabolism*

Substances

  • ferroptosis suppressor protein 1, human
  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Mitochondrial Proteins
  • Reactive Oxygen Species