The Emerging Roles of Ferroptosis in Huntington's Disease

Neuromolecular Med. 2019 Jun;21(2):110-119. doi: 10.1007/s12017-018-8518-6. Epub 2019 Jan 2.

Abstract

Huntington's disease (HD) is an autosomal dominant and fatal neurodegenerative disorder, which is caused by an abnormal CAG repeat in the huntingtin gene. Despite its well-defined genetic origin, the molecular mechanisms of neuronal death are unclear yet, thus there are no effective strategies to block or postpone the process of HD. Ferroptosis, a recently identified iron-dependent cell death, attracts considerable attention due to its putative involvement in neurodegenerative diseases. Accumulative data suggest that ferroptosis is very likely to participate in HD, and inhibition of the molecules and signaling pathways involved in ferroptosis can significantly eliminate the symptoms and pathology of HD. This review first describes evidence for the close relevance of ferroptosis and HD in patients and mouse models, then summarizes advances for the mechanisms of ferroptosis involved in HD, finally outlines some therapeutic strategies targeted ferroptosis. Comprehensive understanding of the emerging roles of ferroptosis in the occurrence of HD will help us to explore effective therapies for slowing the progression of this disease.

Keywords: Ferroptosis; Huntington’s disease; Iron accumulation; Lipid peroxidation; Mutant Huntingtin.

Publication types

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

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Disease Models, Animal
  • Ferroptosis* / drug effects
  • Ferroptosis* / physiology
  • Humans
  • Huntingtin Protein / metabolism
  • Huntington Disease / metabolism
  • Huntington Disease / physiopathology*
  • Huntington Disease / therapy
  • Iron / metabolism
  • Iron Chelating Agents / pharmacology
  • Lipid Peroxidation
  • Mice
  • Mice, Transgenic
  • NF-E2-Related Factor 2 / physiology
  • Neuroglia / metabolism
  • Neurons / metabolism
  • Phospholipid Hydroperoxide Glutathione Peroxidase / deficiency
  • Phospholipid Hydroperoxide Glutathione Peroxidase / physiology

Substances

  • Antioxidants
  • HTT protein, human
  • Htt protein, mouse
  • Huntingtin Protein
  • Iron Chelating Agents
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Iron
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • glutathione peroxidase 4, mouse