It's a notable set of findings, not least because it suggests a way that glycogen and tau aggregation could be tackled in the brain. The researchers also developed a drug based around the 8-Br-cAMP ...

Identification of pygl-1/Glycogen phosphorylase as a regulator of glycolysis in the C. elegans hypodermis. Credit: Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2509003122 ...

When glycogen can’t be broken down, neurons lose a vital defense against oxidative stress—a form of cellular damage tied to aging and disease. That’s where a key enzyme comes in.

However, boosting a particular enzyme, glycogen phosphorylase (GlyP), can get the ball rolling and clear out that excess sugar, in turn stopping tau from clinging to it.

Kapahi says this study not only highlights glycogen metabolism as an unexpected hero in the brain but also opens up a new direction in the search for treatments against Alzheimer's and related ...

More information: Neuronal Glycogen Breakdown Mitigates Tauopathy via Pentose Phosphate Pathway-Mediated Oxidative Stress Reduction, Nature Metabolism (2025). DOI: 10.1038/s42255-025-01314-w ...

Glycogen phosphorylase (GlyP) An enzyme that breaks down glycogen into glucose-1-phosphate. This is the first step in making stored sugar available for metabolic processes. Failure to degrade glycogen ...

When glycogen cannot be broken down, neurons cannot manage oxidative stress, worsening neurodegeneration, however, increasing enzyme glycogen phosphorylase (GlyP) clears excess sugar and stops tau ...

The results could explain why GLP-1 drugs, now widely used for weight loss, show promise against dementia. Glycogen is typically thought of as a reserve energy source stored in the liver and muscles.