Iron dysregulation in Friedreich ataxia.
Friedreich ataxia is the most common hereditary ataxia. The signs and symptoms of the disorder derive from decreased expression of the protein frataxin, which is involved in iron metabolism. Frataxin chaperones iron for iron-sulfur cluster biogenesis and detoxifies iron in the mitochondrial matrix. Decreased expression of frataxin is associated with impairments of iron-sulfur cluster biogenesis and heme synthesis, as well as with mitochondrial dysfunction and oxidative stress. Compounds currently in clinical trials are directed toward improving mitochondrial function and lessening oxidative stress. Iron chelators and compounds that increase frataxin expression are under evaluation. Further elucidation of frataxin's function should lead to additional therapeutic approaches.
Wilson
Robert B
RB
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19106, USA. wilsonr@mail.med.upenn.edu
D000595:Amino Acid Sequence; D000818:Animals; D005621:Friedreich Ataxia / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D006418:Heme / Q000096:biosynthesis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism; D008345:Manganese / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010101:Oxygen Consumption / Q000502:physiology; D013455:Sulfur / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000096923:Frataxin
D006418:Heme; D007501:Iron; D033862:Iron-Binding Proteins; D008345:Manganese; D013455:Sulfur; D013482:Superoxide Dismutase; D000096923:Frataxin