2024-03-29T10:50:03Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/940312017-10-06T07:48:26Zcom_10261_109com_10261_1com_10261_89com_10261_3col_10261_362col_10261_342
Deferiprone and idebenone rescue frataxin depletion phenotypes in a Drosophila model of Friedreich's ataxia
Soriano, Sirena
Llorens, José V.
Blanco-Sobero, Laura
Gutiérrez, Lucía
Calap-Quintana, Pablo
Morales, M. P.
Moltó, María D.
Martínez-Sebastián, María J.
Climbing capability
Life span
Oxidative stress
Mitochondria
Aconitase
Frataxin
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 mitochondrial 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.
This work was supported by a grant from La Fundació la Marató TV3 [exp 101932] of Spain. S.S. is a recipient of a fellowship from Ministerio de Ciencia e Innovación of Spain; J.V.L. is supported by the European Friedreich's Ataxia Consortium for Translational Studies; L.B-S. was a recipient of the fellowship “Cinc Segles-Empresa” from Valencia University, Spain; P.C-Q. is supported by a grant from La Fundació la Marató TV3 of Spain and L.G. holds a Sara Borrell contract from the Spanish ISCIII-MSPS [CD09/00030].
Peer Reviewed
2014-03-21T12:52:17Z
2014-03-21T12:52:17Z
2013
2014-03-21T12:52:18Z
artículo
http://purl.org/coar/resource_type/c_6501
doi: 10.1016/j.gene.2013.02.049
issn: 0378-1119
e-issn: 1879-0038
Gene 521(2): 274-281 (2013)
http://hdl.handle.net/10261/94031
10.1016/j.gene.2013.02.049
none
Elsevier