Iron homeostasis and neurodegeneration in the ageing brain: Insight into ferroptosis pathways

Ageing Res Rev. 2024 Dec:102:102575. doi: 10.1016/j.arr.2024.102575. Epub 2024 Nov 7.

Abstract

Ageing is a major risk factor for various chronic diseases and offers a potential target for developing novel and broadly effective preventatives or therapeutics for age-related conditions, including those affecting the brain. Mechanisms contributing to ageing have been summarized as the hallmarks of ageing, with iron imbalance being one of the major factors. Ferroptosis, an iron-mediated lipid peroxidation-induced programmed cell death, has recently been implicated in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Addressing ferroptosis offers both opportunities and challenges for treating neurodegenerative diseases, though the specific mechanisms remain unclear. This research explores the key processes behind how ferroptosis contributes to brain ageing, with a focus on the complex signaling networks that are involved. The current article aims to uncover that how ferroptosis, a specific type of cell death, may drive age-related changes in the brain. Additionally, the article also unveils its role in neurodegenerative diseases, discussing how understanding these mechanisms could open up new therapeutic avenues.

Keywords: Ageing; Alzheimer’s disease; Ferroptosis; Iron Homeostasis; Neurodegenerative disease.

Publication types

  • Review

MeSH terms

  • Aging* / metabolism
  • Aging* / pathology
  • Aging* / physiology
  • Animals
  • Brain* / metabolism
  • Brain* / pathology
  • Ferroptosis* / physiology
  • Homeostasis* / physiology
  • Humans
  • Iron* / metabolism
  • Neurodegenerative Diseases* / metabolism
  • Neurodegenerative Diseases* / pathology
  • Signal Transduction / physiology

Substances

  • Iron