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Chemical approaches to understanding O-GlcNAc glycosylation in the brain.

Rexach JE, Clark PM, Hsieh-Wilson LC

Division of Chemistry and Chemical Engineering, and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA.

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.

Published 18 January 2008 in Nat Chem Biol, 4(2): 97-106.
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