title: The emerging link between O-GlcNAc and Alzheimer disease.
abstract: Regional glucose hypometabolism is a defining feature of Alzheimer disease (AD). One emerging link between glucose hypometabolism and progression of AD is the nutrient-responsive post-translational O-GlcNAcylation of nucleocytoplasmic proteins. O-GlcNAc is abundant in neurons and occurs on both tau and amyloid precursor protein. Increased brain O-GlcNAcylation protects against tau and amyloid-β peptide toxicity. Decreased O-GlcNAcylation occurs in AD, suggesting that glucose hypometabolism may impair the protective roles of O-GlcNAc within neurons and enable neurodegeneration. Here, we review how O-GlcNAc may link cerebral glucose hypometabolism to progression of AD and summarize data regarding the protective role of O-GlcNAc in AD models.
authors.affiliation: From the Departments of Molecular Biology and Biochemistry and Chemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: From the Departments of Molecular Biology and Biochemistry and.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Shan
authors.affiliation: From the Departments of Molecular Biology and Biochemistry and.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Yuzwa
authors.affiliation: From the Departments of Molecular Biology and Biochemistry and Chemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada dvocadlo@sfu.ca.
authors.forename: David J
authors.initials: DJ
authors.lastname: Vocadlo
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D005947:Glucose / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins; D005947:Glucose; D000117:Acetylglucosamine
keywords: Alzheimer Disease; Amyloid-β (Aβ); Brain Metabolism; Glucose Metabolism; Glycobiology; Glycoprotein; Glycosylation; O-GlcNAcylation; O-Linked N-Acetylglucosamine (O-GlcNAc); Tau Protein (Tau)