O-GlcNAcylation and neurodegeneration

Willayat Y. Wani, John C. Chatham, Victor Darley-Usmar, Lori L. McMahon, Jianhua Zhang*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

88 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)80-87
Number of pages8
JournalBrain Research Bulletin
Volume133
DOIs
StatePublished - Jul 2017

Funding

Keywords

  • Aging
  • Amyloid
  • Autophagy
  • Huntingtin
  • OGA
  • OGT
  • Synuclein
  • Tau

ASJC Scopus subject areas

  • General Neuroscience

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