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O‐GlcNAcylation: A regulator of tau pathology and neurodegeneration
Author(s) -
Gong ChengXin,
Liu Fei,
Iqbal Khalid
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.02.011
Subject(s) - neurodegeneration , neuroprotection , regulator , phosphorylation , intracellular , neuroscience , biology , microbiology and biotechnology , chemistry , biochemistry , disease , medicine , gene
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.