O-GlcNAcylation and neurodegeneration

Academic Article


  • 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.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Wani WY; Chatham JC; Darley-Usmar V; McMahon LL; Zhang J
  • Start Page

  • 80
  • End Page

  • 87
  • Volume

  • 133