The lead author of a new study believes “our brain’s hidden sugar code could unlock powerful tools for combating dementia”
Brits with a sweet-tooth might actively try to curb temptation when they feel they have been raiding the cupboards or sweetie drawer too much. However, did you know sugar could actually hold a major brain benefit?
Scientists have uncovered a surprising sugar-related mechanism inside brain cells that could transform how we fight Alzheimer’s and other dementias.
In Scotland, an estimated 90,000 people are living with dementia, and approximately 66 per cent of those have Alzheimer’s disease, according to Alzheimer’s Research UK.
Now, a new study from scientists at the Buck Institute for Research on Aging has revealed a surprising player in the battle against Alzheimer’s disease and other forms of dementia – brain sugar metabolism.
Published in Nature Metabolism, the research uncovers how breaking down glycogen – a stored form of glucose – in neurons may protect the brain from toxic protein build-up and degeneration.
Glycogen is typically thought of as a reserve energy source stored in the liver and muscles. While small amounts also exist in the brain, its role in neurons has long been dismissed.
“This new study challenges that view, and it does so with striking implications,” says Professor Pankaj Kapahi, PhD, senior scientist on the study. “Stored glycogen doesn’t just sit there in the brain; it is involved in pathology.”
The researchers discovered that in both fly and human models of tauopathy (a group of neurodegenerative diseases including Alzheimer’s), neurons accumulate excessive glycogen.
More importantly, this build-up appears to contribute to disease progression. But tau, the protein that clumps into tangles in Alzheimer’s patients, appears to physically bind to glycogen, trapping it and preventing its breakdown.
When glycogen can’t be broken down, the neurons lose an essential mechanism for managing oxidative stress, a key feature in aging and neurodegeneration. By restoring the activity of an enzyme called glycogen phosphorylase (GlyP), researchers found they could reduce tau-related damage in fruit flies and human stem cell-derived neurons.
“By increasing GlyP activity, the brain cells could better detoxify harmful reactive oxygen species, thereby reducing damage and even extending the lifespan of tauopathy model flies,” said postdoc Sudipta Bar.
Even more promising, the team demonstrated that restricting one’s diet naturally enhanced GlyP activity and improved tau-related outcomes in flies. They further mimicked these effects and showed that the benefits of DR might be reproduced through drug-based activation of this sugar-clearing system.
“This work could explain why GLP-1 drugs, now widely used for weight loss, show promise against dementia, potentially by mimicking dietary restriction,” said Kapahi.
“Work in this simple animal allowed us to move into human neurons in a much more targeted way.”
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 diseases.
“As we continue to age as a society, findings like these offer hope that better understanding – and perhaps rebalancing – our brain’s hidden sugar code could unlock powerful tools for combating dementia,” he added.
