title: O-GlcNAcylation and neurodegeneration.
abstract: O-GlcNAcylation is a dynamic form of protein glycosylation which involves the addition of β-d-N-acetylglucosamine (GlcNAc) via an O-linkage to serine or threonine residues of nuclear, cytoplasmic, mitochondrial and transmembrane proteins. The two enzymes responsible for O-GlcNAc cycling are O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA); their expression and activities in brain are age dependent. More than 1000 O-GlcNAc protein targets have been identified which play critical roles in many cellular processes. In mammalian brain, O-GlcNAc modification of Tau decreases its phosphorylation and toxicity, suggesting a neuroprotective role of pharmacological elevation of brain O-GlcNAc for Alzheimer's disease treatment. Other observations suggest that elevating O-GlcNAc levels may decrease protein clearance or induce apoptosis. This review highlights some of the key findings regarding O-GlcNAcylation in models of neurodegenerative diseases.
authors: Center for Free Radical Biology, Developmental and Integrative Biology, University of Alabama at Birmingham, United States; Department of Pathology, Developmental and Integrative Biology, University of Alabama at Birmingham, United States.
authors: Willayat Y
authors: WY
authors: Wani
authors: Center for Free Radical Biology, Developmental and Integrative Biology, University of Alabama at Birmingham, United States; Department of Pathology, Developmental and Integrative Biology, University of Alabama at Birmingham, United States.
authors: John C
authors: JC
authors: Chatham
authors: Center for Free Radical Biology, Developmental and Integrative Biology, University of Alabama at Birmingham, United States; Department of Pathology, Developmental and Integrative Biology, University of Alabama at Birmingham, United States.
authors: Victor
authors: V
authors: Darley-Usmar
authors: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham,United States.
authors: Lori L
authors: LL
authors: McMahon
authors: Center for Free Radical Biology, Developmental and Integrative Biology, University of Alabama at Birmingham, United States; Department of Pathology, Developmental and Integrative Biology, University of Alabama at Birmingham, United States; Department of Veterans Affairs, Birmingham VA Medical Center, United States. Electronic address: zhanja@uab.edu.
authors: Jianhua
authors: J
authors: Zhang
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000215:Acylation; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics / Q000378:metabolism*
chemical_list: D011506:Proteins; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D006026:Glycoside Hydrolases; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; D000117:Acetylglucosamine
keywords: Aging; Amyloid; Autophagy; Huntingtin; OGA; OGT; Synuclein; Tau