Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance

Fourcade, Stéphane; Morató, Laia; Parameswaran, Janani, 1990-; Ruiz, Montserrat; Ruiz Cortés, Tatiana; Jové, Mariona; Naudí, Alba; Martínez Redondo, Paloma; Dierssen, Mara; Ferrer, Isidre; Villarroya, Francesc; Pamplona, Reinald; Vaquero, Alejandro; Portero Otín, Manuel; Pujol, Aurora, 1968-

Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance

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dc.contributor.author Fourcade, Stéphaneca
dc.contributor.author Morató, Laiaca
dc.contributor.author Parameswaran, Janani, 1990-ca
dc.contributor.author Ruiz, Montserratca
dc.contributor.author Ruiz Cortés, Tatianaca
dc.contributor.author Jové, Marionaca
dc.contributor.author Naudí, Albaca
dc.contributor.author Martínez Redondo, Palomaca
dc.contributor.author Dierssen, Maraca
dc.contributor.author Ferrer, Isidreca
dc.contributor.author Villarroya, Francescca
dc.contributor.author Pamplona, Reinaldca
dc.contributor.author Vaquero, Alejandroca
dc.contributor.author Portero Otín, Manuelca
dc.contributor.author Pujol, Aurora, 1968-ca
dc.date.accessioned 2018-05-15T07:15:26Z
dc.date.available 2018-05-15T07:15:26Z
dc.date.issued 2018
dc.description.abstract Sirtuin 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.
dc.description.sponsorship This 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.
dc.format.mimetype application/pdf
dc.identifier.citation Fourcade S, Morató L, Parameswaran J, Ruiz M, Ruiz-Cortés T, Jové M et al. Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance. Aging Cell. 2017 Dec;16(6):1404-13. DOI: 10.1111/acel.12682
dc.identifier.doi http://dx.doi.org/10.1111/acel.12682
dc.identifier.issn 1474-9718
dc.identifier.uri http://hdl.handle.net/10230/34633
dc.language.iso eng
dc.publisher Wileyca
dc.relation.ispartof Aging Cell. 2017 Dec;16(6):1404-13
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011‐25860
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2014‐55964-R
dc.rights © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Aging
dc.subject.keyword Axonal degeneration
dc.subject.keyword Mitochondria
dc.subject.keyword Redox dyshomeostasis
dc.subject.keyword Sirtuin
dc.title Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalanceca
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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