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dc.contributor.authorFourcade, Stéphane
dc.contributor.authorMorató, Laia
dc.contributor.authorParameswaran, Janani
dc.contributor.authorRuiz, Montserrat
dc.contributor.authorRuiz-Cortés, Tatiana
dc.contributor.authorJové Font, Mariona
dc.contributor.authorNaudí i Farré, Alba
dc.contributor.authorMartínez, Paloma
dc.contributor.authorDierssen, Mara
dc.contributor.authorFerrer, Isidre
dc.contributor.authorVillarroya, Francesc
dc.contributor.authorPamplona Gras, Reinald
dc.contributor.authorVaquero, Alejandro
dc.contributor.authorPortero Otín, Manuel
dc.contributor.authorPujol, Aurora
dc.date.accessioned2018-01-09T11:05:18Z
dc.date.available2018-01-09T11:05:18Z
dc.date.issued2017
dc.identifier.issn1474-9718
dc.identifier.urihttp://hdl.handle.net/10459.1/62312
dc.description.abstractSirtuin 2 (SIRT2) is a member of a family of NAD+-dependent histone deacetylases (HDAC) that play diverse roles in cellular metabolism and especially for aging process. SIRT2 is located in the nucleus, cytoplasm, and mitochondria, is highly expressed in the central nervous system (CNS), and has been reported to regulate a variety of processes including oxidative stress, genome integrity, and myelination. However, little is known about the role of SIRT2 in the nervous system specifically during aging. Here, we show that middle-aged, 13-month-old mice lacking SIRT2 exhibit locomotor dysfunction due to axonal degeneration, which was not present in young SIRT2 mice. In addition, these Sirt2−/− mice exhibit mitochondrial depletion resulting in energy failure, and redox dyshomeostasis. Our results provide a novel link between SIRT2 and physiological aging impacting the axonal compartment of the central nervous system, while supporting a major role for SIRT2 in orchestrating its metabolic regulation. This underscores the value of SIRT2 as a therapeutic target in the most prevalent neurodegenerative diseases that undergo with axonal degeneration associated with redox and energetic dyshomeostasis.ca_ES
dc.description.sponsorshipThis study was supported by grants from the Spanish Institute for Health Carlos III and ‘Fondo Europeo de Desarrollo Regional (FEDER), Union Europea, una manera de hacer Europa’ [FIS PI11/01043, FIS PI14/00410], the Autonomous Government of Catalonia [SGR 2014SGR1430] to A.P., The Spanish Institute for Health Carlos III and ‘Fondo Europeo de Desarrollo Regional (FEDER), Union Europea, una manera de hacer Europa’ [Miguel Servet program CP11/00080, CPII16/00016, FIS PI15/ 00857] to S.F. and the Center for Biomedical Research on Rare Diseases (CIBERER) to M.R., and the Spanish Institute for Health Carlos III and FEDER funds from European Union (‘A way to build Europe’) [FIS grants PI14/01115, PI13/00584, and PI14/00328], Foundation La Marató de TV3 [345/C/2014], and the Autonomous Government of Catalonia [2014SGR168] to M.J., M.P.O., and R.P. The studies conducted at the Chromatin Biology Laboratory were supported by the Spanish Ministry of Economy and Competitiveness-MINECO [SAF2011-25860, SAF2014-55964R] to A.V.ca_ES
dc.language.isoengca_ES
dc.publisherWileyca_ES
dc.relationMICINN/PN2008-2011/SAF2011-25860
dc.relationMINECO/PN2013-2016/SAF2014-55964-R
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1111/acel.12682ca_ES
dc.relation.ispartofAging Cell, 2017, vol. 16, núm. 6, p. 1404-1413ca_ES
dc.rightscc-by (c) Fourcade et al., 2017ca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAgingca_ES
dc.subjectAxonal degenerationca_ES
dc.subjectMitochondriaca_ES
dc.subjectRedox dyshomeostasisca_ES
dc.titleLoss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalanceca_ES
dc.typearticleca_ES
dc.identifier.idgrec026370
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.identifier.doihttps://doi.org/10.1111/acel.12682


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cc-by (c) Fourcade et al., 2017
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