Molecular insights into Friedreich's ataxia and antioxidant-based therapies.
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease causing limb and gait ataxia and cardiomyopathy. The disease gene encodes a mitochondrial protein of unknown function, frataxin. The loss of functional frataxin is caused by a large GAA trinucleotide expansion in the first intron of the gene, thus impairing gene transcription. The lack of frataxin appears to result primarily in disabled recruitment of early antioxidant defenses, resulting in oxidative insult to the highly sensitive iron-sulfur proteins aconitase and three mitochondrial respiratory chain complexes (I-III). Accordingly, antioxidant-based therapy appears promising in counteracting the course of the disease.
Rötig
Agnès
A
INSERM U393 and Service de Cardiologie pédiatrique, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France. roetig@necker.fr
Sidi
Daniel
D
Munnich
Arnold
A
Rustin
Pierre
P
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D016227:Benzoquinones / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics*; D005621:Friedreich Ataxia / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism; D033862:Iron-Binding Proteins; D051379:Mice; D014451:Ubiquinone / Q000031:analogs & derivatives; D000096923:Frataxin
D000975:Antioxidants; D016227:Benzoquinones; D002352:Carrier Proteins; D007501:Iron; D033862:Iron-Binding Proteins; D014451:Ubiquinone; D000096923:Frataxin; C036619:idebenone