A common variant in the iron regulatory gene (Hfe) alters the metabolic and transcriptional landscape in brain regions vulnerable to neurodegeneration.

The role of iron dyshomeostasis in neurodegenerative disease has implicated the involvement of genes that regulate brain iron. The homeostatic iron regulatory gene (HFE) has been at the forefront of these studies given the role of the H63D variant (H67D in mice) in increasing brain iron load. Despite iron's role in oxidative stress production, H67D mice have shown robust protection against neurotoxins and improved recovery from intracerebral hemorrhage.

HFE Mutations in Neurodegenerative Disease as a Model of Hormesis.

Common variants in the iron regulatory protein HFE contribute to systematically increased iron levels, yet the effects in the brain are not fully characterized. It is commonly believed that iron dysregulation is a key contributor to neurodegenerative disease due to iron's ability to catalyze reactive oxygen species production. However, whether HFE variants exacerbate or protect against neurodegeneration has been heavily debated.