Ferroptosis: A potential therapeutic target for neurodegenerative diseases

J Biochem Mol Toxicol. 2021 Aug;35(8):e22830. doi: 10.1002/jbt.22830. Epub 2021 May 28.

Abstract

Ferroptosis is a newly identified regulated form of cell death, which is thought to play a major role in neurodegenerative diseases. In this review, we discuss recent studies elucidating the molecular mechanisms involved in the regulation and execution of ferroptotic cell death and also its role in the brain. Ferroptosis is regulated mainly via iron homeostasis, glutathione metabolism, and lipid peroxidation. Ferroptotic cell death and pro-ferroptotic factors are correlated with the etiopathogenesis of Parkinson's disease (PD) and Alzheimer's disease (AD). Ferroptosis and etiological factors act synergistically in PD and AD pathogenesis. Furthermore, several preclinical and clinical studies targeting ferroptosis in PD and AD have also shown positive results. Evidence of ferroptosis in the brain thus gives new insights into understanding neurodegenerative diseases. Ferroptosis studies in the brain are still in their infancy, but the existing pieces of evidence suggest a strong correlation between ferroptotic cell death and neurodegenerative diseases. Thus, ferroptosis might be a promising target for treating neurodegenerative diseases.

Keywords: Alzheimer's disease; Parkinson's disease; anti-ferroptosis; ferroptosis; iron.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / therapy*
  • Ferroptosis*
  • Humans
  • Lipid Peroxidation*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Parkinson Disease / therapy*