Abstract
A prominent feature of Friedreich’s ataxia (FRDA) is the neurodegeneration of the central and peripheral nervous systems, but little information is available about the mechanisms leading to neuronal damage in this pathology. Currently, no treatments delay, prevent, or reverse the inexorable decline that occurs in this condition. Evidence of oxidative damage has been demonstrated in Friedreich’s ataxia, and this damage has been proposed as the origin of the disease. Nevertheless, the role of oxidative stress in FRDA remains debatable. The lack of direct evidence of reactive oxygen species overproduction in FRDA cells and tissues and the failure of exogenous antioxidants to rescue FRDA phenotypes questions the role of oxidative stress in this pathology. For example, the antioxidant “idebenone” ameliorates cardiomyopathy in FRDA patients, but this therapy does not improve neurodegeneration. To date, no known pharmacological treatment with antioxidant properties cures or delays FRDA neuropathology. This review reports and discusses the evidence of oxidative stress in FRDA and focuses on the existing knowledge of the apparent ineffectiveness of antioxidants for the treatment of neuronal damage.
Highlights
Friedreich’s ataxia (FRDA) is an inherited autosomal recessive disorder caused by severely reduced levels of the mitochondrial iron chaperone protein, frataxin, as a result of a large GAA triplet-repeat expansion within the first intron of the frataxin gene
Is oxidative stress a secondary event of disease progression, or does it represent the primary cause of cell damage in the target tissues? If oxidative damage contributes to the pathogenesis of neurodegeneration in FRDA, why are antioxidant therapies unsuccessful in ameliorating nervous system clinical symptoms? This review provides an overview of the oxidative stress findings in FRDA and analyzes the possible role of redox markers in FRDA neuronal damage to delineate the cause of the selective vulnerability of specific neurons to frataxin deficiency and their apparent unresponsiveness to antioxidants
Despite the mounting evidence that oxidative stress is involved in the FRDA neuron damage that contributes to the pathogenesis of this disorder, clear research documenting sites and mechanisms of oxidative stress generation is lacking
Summary
Friedreich’s ataxia (FRDA) is an inherited autosomal recessive disorder caused by severely reduced levels of the mitochondrial iron chaperone protein, frataxin, as a result of a large GAA triplet-repeat expansion within the first intron of the frataxin gene. The similarities of FRDA with vitamin E deficiency suggested from the beginning a role of oxidative damage in the pathogenesis of this disorder [3]. If oxidative damage contributes to the pathogenesis of neurodegeneration in FRDA, why are antioxidant therapies unsuccessful in ameliorating nervous system clinical symptoms? This review provides an overview of the oxidative stress findings in FRDA and analyzes the possible role of redox markers in FRDA neuronal damage to delineate the cause of the selective vulnerability of specific neurons to frataxin deficiency and their apparent unresponsiveness to antioxidants Is oxidative stress a secondary event of disease progression, or does it represent the primary cause of cell damage in the target tissues? If oxidative damage contributes to the pathogenesis of neurodegeneration in FRDA, why are antioxidant therapies unsuccessful in ameliorating nervous system clinical symptoms? This review provides an overview of the oxidative stress findings in FRDA and analyzes the possible role of redox markers in FRDA neuronal damage to delineate the cause of the selective vulnerability of specific neurons to frataxin deficiency and their apparent unresponsiveness to antioxidants
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
