O-GlcNAcylation of Neuronal Proteins: Roles in Neuronal Functions and in Neurodegeneration

Abstract

{O-GlcNAc} is the attachment of {β-N-acetylglucosamine} to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. It is generally not further elongated but exists as a monosaccharide that can be rapidly added or removed. Thousands of proteins involved in gene transcription, protein translation, and degradation as well as the regulation of signal transduction contain {O-GlcNAc.} Brain is one of the tissues where {O-GlcNAc} is most highly expressed and deletion of neuronal {O-GlcNAc} leads to death early in development. {O-GlcNAc} is also important for normal adult brain function, where dynamic processes like learning and memory at least in part depend on the modification of specific proteins by {O-GlcNAc.} Conversely, too much or too little {O-GlcNAc} on other proteins participates in neurodegenerative processes underlying diseases such as Alzheimer's and Parkinson's. In this chapter, we describe the expression and regulation of {O-GlcNAc} in the nervous system.