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 language | English (US) |
|---|---|
| Pages (from-to) | 2152-2163 |
| Number of pages | 12 |
| Journal | FASEB Journal |
| Volume | 24 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2010 |
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Keywords
- Antioxidants
- Frataxin
- Hydrogen peroxide
- Hydroxyl radical
- Superoxide
ASJC Scopus subject areas
- Biochemistry
- Biotechnology
- Genetics
- Molecular Biology
Cite this
Does oxidative stress contribute to the pathology of Friedreich's ataxia? A radical question. / Armstrong, Jeffrey S.; Khdour, Omar; Hecht, Sidney.
In: FASEB Journal, Vol. 24, No. 7, 07.2010, p. 2152-2163.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Does oxidative stress contribute to the pathology of Friedreich's ataxia? A radical question
AU - Armstrong, Jeffrey S.
AU - Khdour, Omar
AU - Hecht, Sidney
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - Antioxidants
KW - Frataxin
KW - Hydrogen peroxide
KW - Hydroxyl radical
KW - Superoxide
UR - http://www.scopus.com/inward/record.url?scp=77954447250&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954447250&partnerID=8YFLogxK
U2 - 10.1096/fj.09-143222
DO - 10.1096/fj.09-143222
M3 - Article
C2 - 20219987
AN - SCOPUS:77954447250
VL - 24
SP - 2152
EP - 2163
JO - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
JF - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
SN - 0892-6638
IS - 7
ER -