Abstract
O-GlcNAc glycosylation is a unique, dynamic form of glycosylation found on intracellular proteins of all multicellular organisms. Studies suggest that O-GlcNAc represents a key regulatory modification in the brain, contributing to transcriptional regulation, neuronal communication and neurodegenerative disease. Recently, several new chemical tools have been developed to detect and study the modification, including chemoenzymatic tagging methods, quantitative proteomics strategies and small-molecule inhibitors of O-GlcNAc enzymes. Here we highlight some of the emerging roles for O-GlcNAc in the nervous system and describe how chemical tools have significantly advanced our understanding of the scope, functional significance and cellular dynamics of this modification.
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Acknowledgements
We thank C.J. Rogers and H.E. Murrey for critical reading of the manuscript. This work was supported in part by grants from the US National Institutes of Health (RO1 GM084724 and F31 NS056525-02 to J.E.R.) and the US National Science Foundation (CHE-0239861).
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Rexach, J., Clark, P. & Hsieh-Wilson, L. Chemical approaches to understanding O-GlcNAc glycosylation in the brain. Nat Chem Biol 4, 97–106 (2008). https://doi.org/10.1038/nchembio.68
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DOI: https://doi.org/10.1038/nchembio.68
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