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dc.contributor.authorBritti, Elena
dc.contributor.authorDelaspre, Fabien
dc.contributor.authorFeldman, Anat
dc.contributor.authorOsborne, Melissa
dc.contributor.authorGreif, Hagar
dc.contributor.authorTamarit Sumalla, Jordi
dc.contributor.authorRos Salvador, Joaquim
dc.description.abstractFriedreich ataxia (FA) is a rare disease caused by deficiency of frataxin, a mitochondrial protein. As there is no cure available for this disease, many strategies have been developed to reduce the deleterious effects of such deficiency. One of these approaches is based on delivering frataxin to the tissues by coupling the protein to trans-activator of transcription (TAT) peptides, which enables cell membranes crossing. In this study, we tested the efficiency of TAT-MTScs-FXN fusion protein to decrease neurodegeneration markers on frataxin-depleted neurons obtained from dorsal root ganglia (DRG), one of the most affected tissues. In mice models of the disease, we tested the ability of TAT-MTScs-FXN to penetrate the mitochondria and its effect on lifespan. In DRG neurons, treatment with TAT-MTScs-FXN increased cell survival, decreased neurite degeneration and reduced apoptotic markers, such as a-fodrin cleavage and caspase 9 activation. Also, we show that heat-shock protein 60 (HSP60), a molecular chaperone targeted to mitochondria, suffered an impaired processing in frataxin-deficient neurons that was relieved by TAT-MTScs-FXN addition. In mice models of the disease, administration of TAT-MTScs-FXN was able to reach muscle mitochondria, restore the activity of the succinate dehydrogenase and produce a significant lifespan increase. These results support the use of TAT-MTScs-FXN as a treatment for Friedreich ataxia.ca_ES
dc.description.sponsorshipThis work was supported by grant SAF2013-44820-R from MINECO (Spain) and by FEDER (Federacion Española de Enfermedades Raras) grant. E.B. received a fellowship from the University of Lleida.ca_ES
dc.publisherWiley Open Accessca_ES
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofJournal of Cellular and Molecular Medicine, 2018, vol. 22, núm. 2, p. 834-848ca_ES
dc.rightscc-by (c) Britti et al., 2018ca_ES
dc.subjectDorsal root ganglia neuronsca_ES
dc.subjectA-fodrin/heat-shock protein 60ca_ES
dc.subjectSuccinate dehydrogenaseca_ES
dc.titleFrataxin-deficient neurons and mice models of Friedreich ataxia are improved by TAT-MTScs-FXN treatmentca_ES

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