Ferroptosis as a mechanism of neurodegeneration in Alzheimer's disease

J Neurochem. 2021 Dec;159(5):804-825. doi: 10.1111/jnc.15519. Epub 2021 Oct 9.

Abstract

Alzheimer's disease (AD) is the most prevalent form of dementia, with complex pathophysiology that is not fully understood. While β-amyloid plaque and neurofibrillary tangles define the pathology of the disease, the mechanism of neurodegeneration is uncertain. Ferroptosis is an iron-mediated programmed cell death mechanism characterised by phospholipid peroxidation that has been observed in clinical AD samples. This review will outline the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD, with implications for disease-modifying therapies.

Keywords: Alzheimer's disease; ferroptosis; iron; phospholipid peroxidation and neurodegeneration.

Publication types

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

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology*
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Brain / drug effects
  • Brain / metabolism*
  • Brain / physiopathology*
  • Ferroptosis / drug effects
  • Ferroptosis / physiology*
  • Humans
  • Iron Chelating Agents / pharmacology
  • Iron Chelating Agents / therapeutic use
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / physiology
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology

Substances

  • Antioxidants
  • Iron Chelating Agents