Abstract

Iron accumulation in the brain and increased oxidative stress are consistent observations in many neurodegenerative diseases. Thus, we have begun examination into gene mutations or allelic variants that could be associated with loss of iron homeostasis. One of the mechanisms leading to iron overload is a mutation in the HFE gene, which is involved in iron metabolism. The 2 most common HFE gene variants are C282Y (1.9%) and H63D (8.9%). The C282Y HFE variant is more commonly associated with hereditary hemochromatosis, which is an autosomal recessive disorder, characterized by iron overload in a number of systemic organs. The H63D HFE variant appears less frequently associated with hemochromatosis, but its role in the neurodegenerative diseases has received more attention. At the cellular level, the HFE mutant protein resulting from the H63D HFE gene variant is associated with iron dyshomeostasis, increased oxidative stress, glutamate release, tau phosphorylation, and alteration in inflammatory response, each of which is under investigation as a contributing factor to neurodegenerative diseases. Therefore, the HFE gene variants are proposed to be genetic modifiers or a risk factor for neurodegenerative diseases by establishing an enabling milieu for pathogenic agents. This review will discuss the current knowledge of the association of the HFE gene variants with neurodegenerative diseases: amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and ischemic stroke. Importantly, the data herein also begin to dispel the long-held view that the brain is protected from iron accumulation associated with the HFE mutations.

Original languageEnglish (US)
Pages (from-to)729S-739S
JournalJournal of Nutrition
Volume141
Issue number4
DOIs
StatePublished - Apr 1 2011

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Neurodegenerative Diseases
Iron
Brain
Genes
Iron Overload
Hemochromatosis
Mutation
Oxidative Stress
Amyotrophic Lateral Sclerosis
Mutant Proteins
Parkinson Disease
Glutamic Acid
Alzheimer Disease
Homeostasis
Stroke
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Nandar, Wint ; Connor, James R. / HFE gene variants affect iron in the brain. In: Journal of Nutrition. 2011 ; Vol. 141, No. 4. pp. 729S-739S.
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HFE gene variants affect iron in the brain. / Nandar, Wint; Connor, James R.

In: Journal of Nutrition, Vol. 141, No. 4, 01.04.2011, p. 729S-739S.

Research output: Contribution to journalArticle

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