Does oxidative stress contribute to the pathology of Friedreich's ataxia? A radical question

Jeffrey S. Armstrong, Omar Khdour, Sidney Hecht

Research output: Contribution to journalReview article

77 Scopus citations

Abstract

Friedreich's ataxia (FRDA) is a hereditary neurodegenerative disease that frequently culminates in cardiac failure at an early age. FRDA is believed to arise from reduced synthesis of the mitochondrial iron chaperone frataxin due to impaired gene transcription, which leads to mitochondrial iron accumulation, dysfunction of mitochondrial Fe-S containing enzymes, and increased Fenton-mediated free radical production. Recent reports have challenged this generally accepted hypothesis, by suggesting that the oxidative stress component in FRDA is minimal and thereby questioning the benefit of antioxidant therapeutic strategies. We suggest that this apparent paradox results from the radically divergent chemistries of the participating reactive oxygen species (ROS), the major cellular subcompartments involved and the overall cellular responses to ROS. In this review, we consider these factors and conclude that oxidative stress does constitute a major contributing factor to FRDA pathology. This reaffirms the idea that the rational design of specific small molecule multifunctional antioxidants will benefit FRDA patients.

Original languageEnglish (US)
Pages (from-to)2152-2163
Number of pages12
JournalFASEB Journal
Volume24
Issue number7
DOIs
StatePublished - Jul 1 2010

Keywords

  • Antioxidants
  • Frataxin
  • Hydrogen peroxide
  • Hydroxyl radical
  • Superoxide

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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