title: Friedreich's ataxia: coenzyme Q10 and vitamin E therapy.
abstract: Since the identification of the genetic mutation causing Friedreich's ataxia (FRDA) our understanding of the mechanisms underlying disease pathogenesis have improved markedly. The genetic abnormality results in the deficiency of frataxin, a protein targeted to the mitochondrion. There is extensive evidence that mitochondrial respiratory chain dysfunction, oxidative damage and iron accumulation play significant roles in the disease mechanism. There remains considerable debate as to the normal function of frataxin, but it is likely to be involved in mitochondrial iron handling, antioxidant regulation, and/or iron sulphur centre regulation. Therapeutic avenues for patients with FRDA are beginning to be explored in particular targeting antioxidant protection, enhancement of mitochondrial oxidative phosphorylation, iron chelation and more recently increasing FRDA transcription. The use of quinone therapy has been the most extensively studied to date with clear benefits demonstrated using evaluations of both disease biomarkers and clinical symptoms, and this is the topic that will be covered in this review.
authors.affiliation: University Department of Clinical Neurosciences, Royal Free and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK. j.cooper@medsch.ucl.ac.uk
authors.forename: J M
authors.initials: JM
authors.lastname: Cooper
authors.forename: A H V
authors.initials: AH
authors.lastname: Schapira
mesh_terms: D000818:Animals; D001259:Ataxia / Q000378:metabolism; D016227:Benzoquinones / Q000627:therapeutic use; D003067:Coenzymes / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D004195:Disease Models, Animal; D005621:Friedreich Ataxia / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D011809:Quinones / Q000378:metabolism; D013997:Time Factors; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D014810:Vitamin E / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D016227:Benzoquinones; D003067:Coenzymes; D011809:Quinones; D014451:Ubiquinone; D014810:Vitamin E; D007501:Iron; C024989:coenzyme Q10; C036619:idebenone; D010100:Oxygen