title: Mitochondrial dysfunction in Friedreich's ataxia: from pathogenesis to treatment perspectives.
abstract: Friedreich's ataxia (FRDA), the most common inherited ataxia, is an autosomal recessive degenerative disorder caused by a GAA triplet expansion or point mutations in the FRDA gene on chromosome 9q13. The FRDA gene product, frataxin, is a widely expressed mitochondrial protein, which is severely reduced in FRDA patients. The demonstration that deficit of frataxin in FRDA is associated with mitochondrial iron accumulation, increased sensitivity to oxidative stress, deficit of respiratory chain complex activities and in vivo impairment of cardiac and skeletal muscle tissue energy metabolism, has established FRDA as a "new" nuclear encoded mitochondrial disease. Pilot studies have shown the potential effect of antioxidant therapy based on idebenone or coenzyme Q10 plus Vitamin E administration in this condition and provide a strong rationale for designing larger randomized clinical trials.
authors.affiliation: Dipartimento di Medicina Clinica e Biotecnologia Applicata, Universitá di Bologna, Policlinico S. Orsola, Italy. lodi@med.unibo.it
authors.forename: R
authors.initials: R
authors.lastname: Lodi
authors.forename: B
authors.initials: B
authors.lastname: Rajagopalan
authors.forename: J L
authors.initials: JL
authors.lastname: Bradley
authors.forename: D J
authors.initials: DJ
authors.lastname: Taylor
authors.forename: J G
authors.initials: JG
authors.lastname: Crilley
authors.forename: P E
authors.initials: PE
authors.lastname: Hart
authors.forename: A M
authors.initials: AM
authors.lastname: Blamire
authors.forename: D
authors.initials: D
authors.lastname: Manners
authors.forename: P
authors.initials: P
authors.lastname: Styles
authors.forename: A H V
authors.initials: AH
authors.lastname: Schapira
authors.forename: J M
authors.initials: JM
authors.lastname: Cooper
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003067:Coenzymes; D019610:Cytoprotection; D005621:Friedreich Ataxia / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D033862:Iron-Binding Proteins; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000473:pathology; D018384:Oxidative Stress; D017354:Point Mutation; D018911:Trinucleotide Repeats; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014810:Vitamin E / Q000627:therapeutic use; D000096923:Frataxin
chemical_list: D000975:Antioxidants; D002352:Carrier Proteins; D003067:Coenzymes; D033862:Iron-Binding Proteins; D014451:Ubiquinone; D014810:Vitamin E; D000096923:Frataxin; C024989:coenzyme Q10