Brain’s Sugar Management Linked to Neuroprotection

New research reveals a surprising role for glycogen—the body’s energy reserve—in protecting against neurodegenerative diseases like Alzheimer’s. A study published in Nature Metabolism demonstrates that glycogen buildup in neurons contributes to tau pathology, a hallmark of these diseases, by hindering the neuron’s ability to manage oxidative stress.

Researchers found that tau protein physically blocks glycogen breakdown, disrupting a critical pathway for generating protective molecules like NADPH and glutathione. Restoring glycogen breakdown via the enzyme GlyP reduced tau-related damage in both fly and human neuron models.

Dietary restriction and pharmacological activation of GlyP showed similar benefits, suggesting a potential therapeutic avenue. Notably, the findings may explain the observed dementia-protective effects of weight loss drugs like GLP-1s, which appear to enhance this sugar-clearing system. The study also confirmed these effects in neurons derived from patients with frontotemporal dementia, strengthening the potential for broad application.

This research highlights a novel strategy for combating age-related cognitive decline by targeting the brain’s internal sugar management system.