Increasing Brain Protein O-GlcNAc-ylation ...
Type de document :
Article dans une revue scientifique
URL permanente :
Titre :
Increasing Brain Protein O-GlcNAc-ylation Mitigates Breathing Defects and Mortality of Tau.P301L Mice
Auteur(s) :
Borghgraef, Peter [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Menuet, Clément [Auteur]
Faculté des Sciences de Marseille
Theunis, Clara [Auteur]
Louis, Justin V. [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Devijver, Herman [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Maurin, Hervé [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Nocca Smet, Caroline [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Lippens, Guy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Hilaire, Gerard [Auteur]
Faculté des Sciences de Marseille
Gijsen, Harrie [Auteur]
Janssen Research & Development
Moechars, Dieder [Auteur]
Janssen Research & Development
Van Leuven, Fred [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Menuet, Clément [Auteur]
Faculté des Sciences de Marseille
Theunis, Clara [Auteur]
Louis, Justin V. [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Devijver, Herman [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Maurin, Hervé [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Nocca Smet, Caroline [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Lippens, Guy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Hilaire, Gerard [Auteur]
Faculté des Sciences de Marseille
Gijsen, Harrie [Auteur]
Janssen Research & Development
Moechars, Dieder [Auteur]
Janssen Research & Development
Van Leuven, Fred [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Titre de la revue :
PLoS One
Numéro :
8
Pagination :
e84442
Date de publication :
2013-12-23
ISSN :
1932-6203
Discipline(s) HAL :
Chimie/Chimie théorique et/ou physique
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biochimie [q-bio.BM]
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biochimie [q-bio.BM]
Résumé en anglais : [en]
The microtubule associated protein tau causes primary and secondary tauopathies by unknown molecular mechanisms. Post-translational O-GlcNAc-ylation of brain proteins was demonstrated here to be beneficial for Tau.P301L ...
Lire la suite >The microtubule associated protein tau causes primary and secondary tauopathies by unknown molecular mechanisms. Post-translational O-GlcNAc-ylation of brain proteins was demonstrated here to be beneficial for Tau.P301L mice by pharmacological inhibition of O-GlcNAc-ase. Chronic treatment of ageing Tau.P301L mice mitigated their loss in body-weight and improved their motor deficits, while the survival was 3-fold higher at the pre-fixed study endpoint at age 9.5 months. Moreover, O-GlcNAc-ase inhibition significantly improved the breathing parameters of Tau.P301L mice, which underpinned pharmacologically the close correlation of mortality and upper-airway defects. O-GlcNAc-ylation of brain proteins increased rapidly and stably by systemic inhibition of O-GlcNAc-ase. Conversely, biochemical evidence for protein Tau.P301L to become O-GlcNAc-ylated was not obtained, nor was its phosphorylation consistently or markedly affected. We conclude that increasing O-GlcNAc-ylation of brain proteins improved the clinical condition and prolonged the survival of ageing Tau.P301L mice, but not by direct biochemical action on protein tau. The pharmacological effect is proposed to be located downstream in the pathological cascade initiated by protein Tau.P301L, opening novel venues for our understanding, and eventually treating the neurodegeneration mediated by protein tau.Lire moins >
Lire la suite >The microtubule associated protein tau causes primary and secondary tauopathies by unknown molecular mechanisms. Post-translational O-GlcNAc-ylation of brain proteins was demonstrated here to be beneficial for Tau.P301L mice by pharmacological inhibition of O-GlcNAc-ase. Chronic treatment of ageing Tau.P301L mice mitigated their loss in body-weight and improved their motor deficits, while the survival was 3-fold higher at the pre-fixed study endpoint at age 9.5 months. Moreover, O-GlcNAc-ase inhibition significantly improved the breathing parameters of Tau.P301L mice, which underpinned pharmacologically the close correlation of mortality and upper-airway defects. O-GlcNAc-ylation of brain proteins increased rapidly and stably by systemic inhibition of O-GlcNAc-ase. Conversely, biochemical evidence for protein Tau.P301L to become O-GlcNAc-ylated was not obtained, nor was its phosphorylation consistently or markedly affected. We conclude that increasing O-GlcNAc-ylation of brain proteins improved the clinical condition and prolonged the survival of ageing Tau.P301L mice, but not by direct biochemical action on protein tau. The pharmacological effect is proposed to be located downstream in the pathological cascade initiated by protein Tau.P301L, opening novel venues for our understanding, and eventually treating the neurodegeneration mediated by protein tau.Lire moins >
Langue :
Anglais
Audience :
Non spécifiée
Établissement(s) :
CNRS
Université de Lille
Université de Lille
Équipe(s) de recherche :
RMN et interactions moléculaires
Date de dépôt :
2020-02-12T15:45:00Z
2021-03-10T07:31:38Z
2021-03-10T07:31:38Z
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