Mitochondrial Dysfunction in Friedreich's Ataxia: From Pathogenesis to Treatment Perspectives |
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| Authors: | R. Lodi B. Rajagopalan J.L. Bradley D.J. Taylor J.G. Crilley P.E. Hart |
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| Affiliation: | 1. Dipartimento di Medicina Clinica e Biotecnologia Applicata, Universita' di Bologna, Policlinico S. Orsola, Via Massareti 9, 40138 Bologna, Italy;2. MRC Biochemical and Clinical Magnetic Resonance Unit, Department of Biochemistry, University of Oxford and Oxford Radcliffe Hospital, Oxford, UK;3. University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UK |
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| 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 Q 10 plus Vitamin E administration in this condition and provide a strong rationale for designing larger randomized clinical trials. |
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| Keywords: | Friedreich's Ataxia Genetics Mitochondria Oxidative Stress Iron Metabolism Cardiomyopathy |
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