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Keywords:

  • huntingtin;
  • Huntington's disease;
  • iron;
  • magnetic resonance imaging;
  • microglia;
  • neurodegeneration

Abstract

Thumbnail image of graphical abstract

Huntington's disease (HD) is one of many neurodegenerative diseases with reported alterations in brain iron homeostasis that may contribute to neuropathogenesis. Iron accumulation in the specific brain areas of neurodegeneration in HD has been proposed based on observations in post-mortem tissue and magnetic resonance imaging studies. Altered magnetic resonance imaging signal within specific brain regions undergoing neurodegeneration has been consistently reported and interpreted as altered levels of brain iron. Biochemical studies using various techniques to measure iron species in human samples, mouse tissue, or in vitro has generated equivocal data to support such an association. Whether elevated brain iron occurs in HD, plays a significant contributing role in HD pathogenesis, or is a secondary effect remains currently unclear.

Huntington's disease (HD) is one of many neurodegenerative diseases reported to have alterations in brain iron homeostasis. Whether elevated brain iron occurs in HD, and whether elevated iron levels play a significant contributory role in HD pathogenesis remains currently unclear. In this review, we discuss potential mechanisms by which mutant huntingtin-mediated increases in intracellular calcium and elevated intracellular iron may interact to result in elevated levels of reactive oxygen species leading to lipid peroxidation, DNA damage, and neuronal cell death.