Friedreich's ataxia is an autosomal recessive neurodegenerative disease that is due to the loss of function of the frataxin protein. The molecular basis of this disease is still a matter of debate and treatments have so far focused on managing symptoms. Drugs that can increase the amount of frataxin protein offer a possible therapy for the disease. One such drug is recombinant human erythropoietin (rhu-EPO). Here, we report the effects of rhu-EPO on frataxin mRNA and protein in primary fibroblast cell cultures derived from Friedreich's ataxia patients.

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The maturation of cytosolic iron-sulfur (Fe/S) proteins in mammalian cells requires components of the mitochondrial iron-sulfur cluster assembly and export machineries. Little is known about the cytosolic components that may facilitate the assembly process. Here, we identified the cytosolic soluble P-loop NTPase termed huNbp35 (also known as Nubp1) as an Fe/S protein, and we defined its role in the maturation of Fe/S proteins in HeLa cells. Depletion of huNbp35 by RNA interference decreased cell growth considerably, indicating its essential function. The deficiency in huNbp35 was associated with an impaired maturation of the cytosolic Fe/S proteins glutamine phosphoribosylpyrophosphate amidotransferase and iron regulatory protein 1 (IRP1), while mitochondrial Fe/S proteins remained intact.

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Evaluation of therapeutic agents for Friedreich Ataxia (FA) has been limited by a lack of adequate markers of disease progression. We assessed the capacity of health related quality of life (HRQOL) questionnaires to reflect disease status in FA. The SF-36 and several symptom-specific scales were administered to an FA cohort. Scores were compared with norms for the United States population, and to a disease-free control group of similar age and gender.

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Friedreich's ataxia is a neurodegenerative disease caused by reduced expression of the mitochondrial protein frataxin. The main phenotypic features of frataxin-deficient human and yeast cells include iron accumulation in mitochondria, iron-sulphur cluster defects and high sensitivity to oxidative stress. Glutathione is a major protective agent against oxidative damage and glutathione-related systems participate in maintaining the cellular thiol/disulfide status and the reduced environment of the cell. Here, we present the first detailed biochemical study of the glutathione-dependent redox status of wild-type and frataxin-deficient cells in a yeast model of the disease. There were five times less total glutathione (GSH+GSSG) in frataxin-deficient cells, imbalanced GSH/GSSG pools and higher glutathione peroxidase activity.

Read More: Glutathione-dependent redox status of frataxin-deficient cells in a yeast model of Friedreich's ataxia