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

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 bee...

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Autores: Fourcade, Stéphane, Morató, Laia, Parameswaran, Janani, Ruiz, Montserrat, Ruiz-Cortés, Tatiana, Jove, Mariona, Naudi, Alba, Martínez Redondo, Paloma, Dierssen, Mara, Ferrer, Isidro (Ferrer Abizanda), Villarroya i Gombau, Francesc, Pamplona, Reinald, Vaquero García, Alejandro, Portero-Otin, Manuel, Pujol Onofre, Aurora
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/127260
Acceso en línea:https://hdl.handle.net/2445/127260
Access Level:acceso abierto
Palabra clave:Envelliment
Mitocondris
Axons
Metabolisme
Locomoció
Fisiologia
Enzims
Aging
Mitochondria
Metabolism
Locomotion
Physiology
Enzymes
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repository_id_str
spelling Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalanceFourcade, StéphaneMorató, LaiaParameswaran, JananiRuiz, MontserratRuiz-Cortés, TatianaJove, MarionaNaudi, AlbaMartínez Redondo, PalomaDierssen, MaraFerrer, Isidro (Ferrer Abizanda)Villarroya i Gombau, FrancescPamplona, ReinaldVaquero García, AlejandroPortero-Otin, ManuelPujol Onofre, AuroraEnvellimentMitocondrisAxonsMetabolismeLocomocióFisiologiaEnzimsAgingMitochondriaAxonsMetabolismLocomotionPhysiologyEnzymesSirtuin 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.John Wiley & Sons2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/127260Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1111/acel.12682Aging Cell, 2017, vol. 16, num. 6, p. 1404-1413https://doi.org/10.1111/acel.12682cc-by (c) Fourcade, Stéphane et al., 2017http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1272602026-05-27T06:46:51Z
dc.title.none.fl_str_mv Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance
title Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance
spellingShingle Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance
Fourcade, Stéphane
Envelliment
Mitocondris
Axons
Metabolisme
Locomoció
Fisiologia
Enzims
Aging
Mitochondria
Axons
Metabolism
Locomotion
Physiology
Enzymes
title_short Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance
title_full Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance
title_fullStr Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance
title_full_unstemmed Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance
title_sort Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance
dc.creator.none.fl_str_mv Fourcade, Stéphane
Morató, Laia
Parameswaran, Janani
Ruiz, Montserrat
Ruiz-Cortés, Tatiana
Jove, Mariona
Naudi, Alba
Martínez Redondo, Paloma
Dierssen, Mara
Ferrer, Isidro (Ferrer Abizanda)
Villarroya i Gombau, Francesc
Pamplona, Reinald
Vaquero García, Alejandro
Portero-Otin, Manuel
Pujol Onofre, Aurora
author Fourcade, Stéphane
author_facet Fourcade, Stéphane
Morató, Laia
Parameswaran, Janani
Ruiz, Montserrat
Ruiz-Cortés, Tatiana
Jove, Mariona
Naudi, Alba
Martínez Redondo, Paloma
Dierssen, Mara
Ferrer, Isidro (Ferrer Abizanda)
Villarroya i Gombau, Francesc
Pamplona, Reinald
Vaquero García, Alejandro
Portero-Otin, Manuel
Pujol Onofre, Aurora
author_role author
author2 Morató, Laia
Parameswaran, Janani
Ruiz, Montserrat
Ruiz-Cortés, Tatiana
Jove, Mariona
Naudi, Alba
Martínez Redondo, Paloma
Dierssen, Mara
Ferrer, Isidro (Ferrer Abizanda)
Villarroya i Gombau, Francesc
Pamplona, Reinald
Vaquero García, Alejandro
Portero-Otin, Manuel
Pujol Onofre, Aurora
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Envelliment
Mitocondris
Axons
Metabolisme
Locomoció
Fisiologia
Enzims
Aging
Mitochondria
Axons
Metabolism
Locomotion
Physiology
Enzymes
topic Envelliment
Mitocondris
Axons
Metabolisme
Locomoció
Fisiologia
Enzims
Aging
Mitochondria
Axons
Metabolism
Locomotion
Physiology
Enzymes
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/127260
url https://hdl.handle.net/2445/127260
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1111/acel.12682
Aging Cell, 2017, vol. 16, num. 6, p. 1404-1413
https://doi.org/10.1111/acel.12682
dc.rights.none.fl_str_mv cc-by (c) Fourcade, Stéphane et al., 2017
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Fourcade, Stéphane et al., 2017
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869412978377359360
score 15.301603

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