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Activation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophy

dc.contributor.authorMorató, Laia
dc.contributor.authorRuiz, M.
dc.contributor.authorBoada Pallàs, Jordi
dc.contributor.authorCalingasan, Noel Ylagan
dc.contributor.authorGalino, Jorge
dc.contributor.authorGuilera, Cristina
dc.contributor.authorJové Font, Mariona
dc.contributor.authorNaudí i Farré, Alba
dc.contributor.authorFerrer, Isidre
dc.contributor.authorPamplona Gras, Reinald
dc.contributor.authorSerrano, M.
dc.contributor.authorPortero Otín, Manuel
dc.contributor.authorBeal, M. F.
dc.contributor.authorFourcade, Stéphane
dc.contributor.authorPujol, Aurora
dc.date.accessioned2016-11-09T10:14:00Z
dc.date.issued2015
dc.identifier.issn1350-9047
dc.identifier.urihttp://hdl.handle.net/10459.1/58437
dc.description.abstractOxidative stress and mitochondrial failure are prominent factors in the axonal degeneration process. In this study, we demonstrate that sirtuin 1 (SIRT1), a key regulator of the mitochondrial function, is impaired in the axonopathy and peroxisomal disease X-linked adrenoleukodystrophy (X-ALD). We have restored SIRT1 activity using a dual strategy of resveratrol treatment or by the moderate transgenic overexpression of SIRT1 in a X-ALD mouse model. Both strategies normalized redox homeostasis, mitochondrial respiration, bioenergetic failure, axonal degeneration and associated locomotor disabilities in the X-ALD mice. These results indicate that the reactivation of SIRT1 may be a valuable strategy to treat X-ALD and other axonopathies in which the control of redox and energetic homeostasis is impaired.ca_ES
dc.description.sponsorshipThis work was supported by grants from the European Commission [FP7-241622], the Spanish Institute for Health Carlos III [FIS PI11/01043], the Oliver’s Army Foundation, the Government of Catalonia [2009SGR85 to AP], the Spanish Institute for Health Carlos III [Miguel Servet program CP11/00080 to S.F.], the European Leukodystrophy Association (ELA) [ELA 2010-020F1 to SF, ELA 2013-003F1 to LM], the Spanish Ministry of Education [FPU program AP2008-03728 to LM]. JG held an IDIBELL PhD fellowship. The studies conducted at the Experimental Medicine Department were supported in part by R+D grants from the Spanish Ministry of Science and Innovation [BFU2009-11879/BFI], the Spanish Ministry of Health [PI081843, PI1300584], the Government of Catalonia [2009SGR735], the 'La Caixa' Foundation and COST B35 Action of the European Union. CIBERER and CIBERNED are initiatives of the Spanish Institute for Health Carlos III.ca_ES
dc.language.isoengca_ES
dc.publisherMacmillan Publishersca_ES
dc.relationMICINN/PN2008-2011/BFU2009-11879/BFI
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1038/cdd.2015.20ca_ES
dc.relation.ispartofCell Death and Differentiation, 2015, vol. 22, p. 1742-1753ca_ES
dc.rights(c) Macmillan Publishers Limited, 2015ca_ES
dc.titleActivation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophyca_ES
dc.typearticleca_ES
dc.identifier.idgrec022612
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.identifier.doihttps://doi.org/10.1038/cdd.2015.20
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/241622
dc.date.embargoEndDate10000-01-01


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