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Updated: Jun 19, 2026
Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes
Published on: December 20, 2019
O-GlcNAc modification and the tauopathies: insights from chemical biology
Scott A Yuzwa1, David J Vocadlo
1Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Dr, Burnaby, BC, V5A 1S6, Canada.
Abstract:
The aggregation of the microtubule-associated protein tau into paired-helical filaments is the defining characteristic of the tauopathies. It has become apparent that the hyperphosphorylation of tau likely plays a role in the aggregation process and thus strategies to reduce tau phosphorylation are generating wide interest. The O-GlcNAc posttranslational modification of tau has been shown to be reciprocal to its phosphorylation; increasing O-GlcNAc leads to reductions in tau phosphorylation. In this mini-review, we highlight the use of chemical compounds as a means of understanding the reciprocal nature of tau phosphorylation and tau O-GlcNAcylation and highlight some recent progress in this area.
Insights
Strategies targeting tau phosphorylation are crucial for tauopathies. Chemical compounds reveal that increasing O-GlcNAc modification of tau reduces its harmful phosphorylation and aggregation.
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Tau aggregation into paired-helical filaments defines tauopathies.
- Hyperphosphorylation of tau is implicated in this aggregation process.
- O-GlcNAcylation is a posttranslational modification of tau.
Purpose of the Study:
- To review the use of chemical compounds in studying tau phosphorylation and O-GlcNAcylation.
- To highlight the reciprocal relationship between tau phosphorylation and O-GlcNAcylation.
- To present recent advancements in this research area.
Main Methods:
- Review of literature on chemical compounds affecting tau modification.
- Analysis of studies demonstrating the reciprocal regulation of tau phosphorylation and O-GlcNAcylation.
- Discussion of recent progress in the field.
Main Results:
- Chemical compounds are valuable tools for investigating the interplay between tau phosphorylation and O-GlcNAcylation.
- Increased O-GlcNAcylation of tau leads to decreased tau phosphorylation.
- This reciprocal relationship offers potential therapeutic strategies for tauopathies.
Conclusions:
- Understanding the reciprocal regulation of tau phosphorylation and O-GlcNAcylation is key to developing treatments for tauopathies.
- Chemical modulators of O-GlcNAcylation show promise in reducing tau phosphorylation.
- Further research into these chemical compounds could lead to novel therapeutic interventions for neurodegenerative diseases.
