Title :

Increasing Brain Protein O-GlcNAc-ylation Mitigates Breathing Defects and Mortality of Tau.P301L Mice

Author(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]

Journal title :

PLoS One

Volume number :

8

Pages :

e84442

Publication date :

2013-12-23

ISSN :

1932-6203

HAL domain(s) :

Chimie/Chimie théorique et/ou physique
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biochimie [q-bio.BM]

English abstract : [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 ...
Show more >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.Show less >

Language :

Anglais

Audience :

Non spécifiée

Administrative institution(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

RMN et interactions moléculaires

Submission date :

2020-02-12T15:45:00Z
2021-03-10T07:31:38Z