title: Activation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophy.
abstract: Oxidative 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.
authors.affiliation: Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Spain.|Center for Biomedical Research on Rare Diseases (CIBERER) ISCIII, Spain.|Institute of Neuropathology, University of Barcelona, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Morató
authors.affiliation: Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Spain.|Center for Biomedical Research on Rare Diseases (CIBERER) ISCIII, Spain.|Institute of Neuropathology, University of Barcelona, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ruiz
authors.affiliation: Experimental Medicine Department, University of Lleida-IRBLleida, 25008 Lleida, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Boada
authors.affiliation: Department of Neurology and Neuroscience, Weill Cornell Medical College, 1006 New York, USA.
authors.forename: N Y
authors.initials: NY
authors.lastname: Calingasan
authors.affiliation: Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Spain.|Center for Biomedical Research on Rare Diseases (CIBERER) ISCIII, Spain.|Institute of Neuropathology, University of Barcelona, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Galino
authors.affiliation: Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Spain.|Center for Biomedical Research on Rare Diseases (CIBERER) ISCIII, Spain.|Institute of Neuropathology, University of Barcelona, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Guilera
authors.affiliation: Experimental Medicine Department, University of Lleida-IRBLleida, 25008 Lleida, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Jové
authors.affiliation: Experimental Medicine Department, University of Lleida-IRBLleida, 25008 Lleida, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Naudí
authors.affiliation: Institute of Neuropathology, University of Barcelona, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.|Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED) ISCIII, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Experimental Medicine Department, University of Lleida-IRBLleida, 25008 Lleida, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Pamplona
authors.affiliation: Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Serrano
authors.affiliation: Experimental Medicine Department, University of Lleida-IRBLleida, 25008 Lleida, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Portero-Otín
authors.affiliation: Department of Neurology and Neuroscience, Weill Cornell Medical College, 1006 New York, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Beal
authors.affiliation: Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Spain.|Center for Biomedical Research on Rare Diseases (CIBERER) ISCIII, Spain.|Institute of Neuropathology, University of Barcelona, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Fourcade
authors.affiliation: Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Spain.|Center for Biomedical Research on Rare Diseases (CIBERER) ISCIII, Spain.|Institute of Neuropathology, University of Barcelona, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.|Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Pujol
mesh_terms: D000326:Adrenoleukodystrophy / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D010084:Oxidation-Reduction; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000627:therapeutic use*
chemical_list: D013267:Stilbenes; D056564:Sirtuin 1; D000077185:Resveratrol
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