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O-GlcNAc cycling: implications for neurodegenerative disorders
Brooke D Lazarus1, Dona C Love, John A Hanover
1Laboratory of Cell Biology and Biochemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
The International Journal of Biochemistry & Cell Biology
|September 29, 2009
Summary
O-linked N-acetylglucosamine (O-GlcNAc) modification regulates cellular processes and is linked to diseases like diabetes and neurodegeneration. This review details the enzymes O-GlcNAc transferase (OGT) and beta-N-acetylglucosaminidase (OGA) involved in this crucial nutrient-sensing pathway.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Signaling
Background:
- O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification regulating numerous cellular functions.
- Dysregulation of O-GlcNAcylation is implicated in diseases such as type-2 diabetes and neurodegenerative disorders.
Purpose of the Study:
- This review focuses on the enzymes O-GlcNAc transferase (OGT) and beta-N-acetylglucosaminidase (OGA) responsible for O-GlcNAc cycling.
- It examines the structural domains, regulated substrates, and cellular processes influenced by OGT and OGA.
- The review emphasizes O-GlcNAc's role as a nutrient sensor impacting insulin signaling, stress response, and neuroendocrine/central nervous system functions.
Main Methods:
- Literature review of O-GlcNAcylation, OGT, and OGA.
- Analysis of enzyme structural domains and their functional implications.
- Synthesis of current knowledge on O-GlcNAc-regulated pathways and disease associations.
Main Results:
- OGT and OGA form a critical enzymatic pair controlling protein O-GlcNAcylation.
- O-GlcNAcylation impacts key cellular processes including transcription, translation, and apoptosis.
- O-GlcNAc acts as a nutrient sensor, influencing insulin signaling and cellular stress responses.
Conclusions:
- Understanding OGT and OGA function is crucial for deciphering O-GlcNAcylation's role in health and disease.
- O-GlcNAc cycling represents a significant link between nutrient availability and cellular signaling.
- Further research into O-GlcNAc's impact on the neuroendocrine and central nervous systems holds therapeutic potential.
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