J Neurol Sci. 2004 Dec 15;227(1):27-33. Related Articles, Links  

Increased incidence of the Hfe mutation in amyotrophic lateral sclerosis and
related cellular consequences.

Wang XS, Lee S, Simmons Z, Boyer P, Scott K, Liu W, Connor J.

Department of Neurosurgery, Penn State College of Medicine, Hershey, PA 17033,
USA.

The etiology of amyotrophic lateral sclerosis (ALS) is unknown. The presence of
mutations in the superoxide dismutase gene (SOD1) has led to theories regarding
a role for oxidative stress in the pathogenesis of this disease. A primary
cause of oxidative stress is perturbations in cellular iron homeostasis.
Cellular iron mismanagement and oxidative stress are associated with a number
of neurodegenerative diseases. One mechanism by which cells fail to properly
regulate their iron status is through a mutation in the Hfe gene. Mutations in
the Hfe gene are associated with the iron overload disease, hemochromatosis. In
the current study, 31% of patients with sporadic ALS carried a mutation in the
Hfe gene, compared to only 14% of patients without identifiable neuromuscular
disease, or with neuromuscular diseases other than ALS (p<0.005). To determine
the cellular consequences of carrying an Hfe mutation, a human neuronal cell
line was transfected with genes carrying the Hfe mutation. The presence of the
Hfe mutation disrupted expression of tubulin and actin at the protein levels
potentially consistent with the disruption of axonal transport seen in ALS and
was also associated with a decrease in CuZnSOD1 expression. These data provide
compelling evidence for a role for the Hfe mutation in etiopathogenesis of ALS
and warrant further investigation.

PMID: 15546588 [PubMed - as supplied by publisher]

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