Journal
GENE
Volume 521, Issue 2, Pages 274-281Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.gene.2013.02.049
Keywords
Frataxin; Aconitase Mitochondria; Oxidative stress; Life span; Climbing capability
Categories
Funding
- La Fundacio la Marato TV3 of Spain [exp 101932]
- Ministerio de Ciencia e Innovacion of Spain
- European Friedreich's Ataxia Consortium for Translational Studies
- Cinc Segles-Empresa from Valencia University, Spain
- Spanish ISCIII-MSPS [CD09/00030]
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Friedreich's ataxia (FRDA), the most common inherited ataxia, is a neurodegenerative disease caused by a reduction in the levels of the mitochondrial protein frataxin, the function of which remains a controversial matter. Several therapeutic approaches are being developed to increase frataxin expression and reduce the intramitochondrial iron aggregates and oxidative damage found in this disease. In this study, we tested separately the response of a Drosophila RNAi model of FRDA (Llorens et al., 2007) to treatment with the iron chelator deferiprone (DFP) and the antioxidant idebenone (IDE), which are both in clinical trials. The FRDA flies have a shortened life span and impaired motor coordination, and these phenotypes are more pronounced in oxidative stress conditions. In addition, under hyperoxia, the activity of the mitochondria( enzyme aconitase is strongly reduced in the FRDA flies. This study reports that DFP and IDE improve the life span and motor ability of frataxin-depleted flies. We show that DFP eliminates the excess of labile iron in the mitochondria and thus prevents the toxicity induced by iron accumulation. IDE treatment rescues aconitase activity in hyperoxic conditions. These results validate the use of our Drosophila model of FRDA to screen for therapeutic molecules to treat this disease. (C) 2013 Elsevier B.V. All rights reserved.
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