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

Xin Sheng Wang, Sang Lee, Zachary Simmons, Philip Boyer, Kevin Scott, Wenlei Liu, James Connor

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)27-33
Number of pages7
JournalJournal of the neurological sciences
Volume227
Issue number1
DOIs
StatePublished - Dec 15 2004

Fingerprint

Amyotrophic Lateral Sclerosis
Mutation
Incidence
Neuromuscular Diseases
Oxidative Stress
Iron
Genes
Axonal Transport
Iron Overload
Hemochromatosis
Tubulin
Neurodegenerative Diseases
Superoxide Dismutase
Actins
Homeostasis
Cell Line

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

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title = "Increased incidence of the Hfe mutation in amyotrophic lateral sclerosis and related cellular consequences",
abstract = "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.",
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Increased incidence of the Hfe mutation in amyotrophic lateral sclerosis and related cellular consequences. / Wang, Xin Sheng; Lee, Sang; Simmons, Zachary; Boyer, Philip; Scott, Kevin; Liu, Wenlei; Connor, James.

In: Journal of the neurological sciences, Vol. 227, No. 1, 15.12.2004, p. 27-33.

Research output: Contribution to journalArticle

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AU - Liu, Wenlei

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