The roles of iron and HFE genotype in neurological diseases

Mol Aspects Med. 2020 Oct:75:100867. doi: 10.1016/j.mam.2020.100867. Epub 2020 Jul 9.

Abstract

Iron accumulation is a recurring pathological phenomenon in many neurological diseases including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and others. Iron is essential for normal development and functions of the brain; however, excess redox-active iron can also lead to oxidative damage and cell death. Especially for terminally differentiated cells like neurons, regulation of reactive oxygen species is critical for cell viability. As a result, cellular iron level is tightly regulated. Although iron accumulation related to neurological diseases has been well documented, the pathoetiological contributions of the homeostatic iron regulator (HFE), which controls cellular iron uptake, is less understood. Furthermore, a common HFE variant, H63D HFE, has been identified as a modifier of multiple neurological diseases. This review will discuss the roles of iron and HFE in the brain as well as their impact on various disease processes.

Keywords: HFE; Iron; Neurological diseases.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease
  • Genotype
  • Hemochromatosis Protein / genetics*
  • Hemochromatosis Protein / metabolism
  • Humans
  • Iron
  • Nervous System Diseases* / genetics
  • Oxidative Stress

Substances

  • HFE protein, human
  • Hemochromatosis Protein
  • Iron