title: O-GlcNAcylation: A regulator of tau pathology and neurodegeneration.
abstract: O-GlcNAcylation is the posttranslational modification of intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). The discovery of O-GlcNAc modification of tau and its impact on tau phosphorylation has attracted recent research interest in O-GlcNAc studies in the Alzheimer's disease (AD) field. Modification of proteins by O-GlcNAc occurs extensively in the brain. The expressions and activities of the enzymes catalyzing O-GlcNAc cycling are several-fold higher in the brain than in the peripheral tissues. The O-GlcNAcylation levels of brain proteins including tau are decreased in AD brain, probably due to decreased brain glucose metabolism. The reduction of brain O-GlcNAcylation appears to mediate the molecular mechanism by which decreased brain glucose metabolism contributes to neurodegeneration. Studies on mouse models of tauopathies suggest a neuroprotective role of pharmacological elevation of brain O-GlcNAc, which could potentially be a promising approach for treating AD and other neurodegenerative diseases.
authors.affiliation: Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA. Electronic address: Chengxin.Gong@csi.cuny.edu.
authors.forename: Cheng-Xin
authors.initials: CX
authors.lastname: Gong
authors.affiliation: Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D024801:Tauopathies / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D005947:Glucose; D000117:Acetylglucosamine
keywords: Alzheimer's disease; Hyperphosphorylation; Neurodegeneration; O-GlcNAcylation; Tau