title: Dysregulation of the nutrient/stress sensor O-GlcNAcylation is involved in the etiology of cardiovascular disorders, type-2 diabetes and Alzheimer's disease.
abstract: O-GlcNAcylation is widespread within the cytosolic and nuclear compartments of cells. This post-translational modification is likely an indicator of good health since its intracellular level correlates with the availability of extracellular glucose. Apart from its status as a nutrient sensor, O-GlcNAcylation may also act as a stress sensor since it exerts its fundamental effects in response to stress. Several studies report that the cell quickly responds to an insult by elevating O-GlcNAcylation levels and by unmasking a newly described Hsp70-GlcNAc binding property. From a more practical point of view, it has been shown that O-GlcNAcylation impairments contribute to the etiology of cardiovascular diseases, type-2 diabetes and Alzheimer's disease (AD), three illnesses common in occidental societies. Many studies have demonstrated that O-GlcNAcylation operates as a powerful cardioprotector and that by raising O-GlcNAcylation levels, the organism more successfully resists trauma-hemorrhage and ischemia/reperfusion injury. Recent data have also shown that insulin resistance and, more broadly, type-2 diabetes can be controlled by O-GlcNAcylation of the insulin pathway and O-GlcNAcylation of the gluconeogenesis transcription factors FoxO1 and CRCT2. Lastly, the finding that AD may correspond to a type-3 diabetes offers new perspectives into the knowledge of the neuropathology and into the search for new therapeutic avenues.
authors.affiliation: CNRS-UMR 8576, Unit of Structural and Functional Glycobiology, IFR 147, University of Lille 1, Villeneuve d'Ascq, France. tony.lefebvre@univ-lille1.fr
authors.forename: Tony
authors.initials: T
authors.lastname: Lefebvre
authors.forename: Vanessa
authors.initials: V
authors.lastname: Dehennaut
authors.forename: Céline
authors.initials: C
authors.lastname: Guinez
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Olivier
authors.forename: Ludivine
authors.initials: L
authors.lastname: Drougat
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mir
authors.forename: Marlène
authors.initials: M
authors.lastname: Mortuaire
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Vercoutter-Edouart
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Michalski
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D001921:Brain / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014452:Ubiquitins / Q000502:physiology
chemical_list: D000117:Acetylglucosamine; D051792:Basic Helix-Loop-Helix Proteins; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D005947:Glucose; D018840:HSP70 Heat-Shock Proteins; D018398:Homeodomain Proteins; D017351:N-Acetylglucosaminyltransferases; D046988:Proteasome Endopeptidase Complex; D015534:Trans-Activators; D014157:Transcription Factors; D014452:Ubiquitins; C493245:CRTC2 protein, human; C085126:FOXO1 protein, human; C093970:NEUROD1 protein, human; C084010:pancreatic and duodenal homeobox 1 protein