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Friedreich's ataxia

par Pandolfo, Massimo
Editeur scientifique Wells, Robert D.;Ashizawa, Tetsuo
Référence Genetic Instabilities and Neurological Diseases, Academic Press, Burlington, Ed. 2, page (277-296)
Publication Publié, 2006

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Résumé :

This chapter discusses Friedreich's ataxia, the most frequent cause of inherited ataxia in Caucasians. The disease is, in most cases, due to a large expansion of an intronic GAA repeat, resulting in decreased expression of the target frataxin gene. The autosomal recessive inheritance of the disease gives this triplet-repeat mutation some unique features of natural history and evolution. The frataxin gene encodes a mitochondrial protein that has homologs in all eukaryotes and in gram-negative bacteria. Studies in yeast, mouse models, and biochemical investigations indicate a role for frataxin in the assembly of iron-sulfur clusters in the mitochondrion. Frataxin deficiency leads to abnormal mitochondrial iron metabolism, decreased activities of iron-sulfur cluster-containing enzymes, reduced oxidative phosphorylation, and possibly increased oxidative stress. The basis of the specific cell vulnerability observed in Friedreich's ataxia is still unclear. An increasing knowledge of pathogenetic mechanisms allows the proposal of novel treatment approaches. © 2006 Elsevier Inc. All rights reserved.