The role of sugars in protecting the brain

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For years, scientists studying brain aging have focused on proteins and DNA. But what if a crucial piece of the puzzlehas been overlooked?

A team of researchers at Stanford University has shifted its focus to sugar molecules that coat cells in the brain, revealing a new factor in cognitive decline and diseases like Alzheimer’s.

Every cell in the body is covered by a layer of complex sugar chains, forming a protective shield called the glycocalyx. This coating plays a critical role in cell communication and defense, yet it has been largely ignored in brain research.

Dr. Carolyn Bertozzi, a Nobel Prize-winning chemistry professor, describes the study as an entirely new way of looking at the brain:

“This is like landing on a new planet. We’re stepping outside for the first time and trying to make sense of what’s out there.”

The research, led by Stanford Bio-X Graduate Fellow Sophia Shi, focused on how the glycocalyx affects the blood-brain barrier—a protective structure that filters harmful substances from reaching the brain.

What Happens to the Brain’s Sugar Shield as We Age?

Using aging mice, Shi’s study revealed dramatic changes in the glycocalyx over time. In young, healthy brains, the glycocalyx is like a dense and thriving forest.

But in older brains, it becomes thin and patchy, weakening the blood-brain barrier and allowing harmful molecules to seep in. This breakdown may contribute to inflammation, cognitive decline, and neurodegenerative diseases.

Dr. Tony Wyss-Coray, a neurology professor and study co-author, emphasizes the importance of these findings:

“This work lays the foundation for a new field of inquiry into how the aging brain loses its resilience.”

One of the most exciting discoveries was that reintroducing key sugar-coated proteins (mucins) in older mice helped restore the glycocalyx, strengthening the blood-brain barrier and improving memory and brain function.

Shi explains:

“Modulating glycans has a major effect on the brain—both negatively in aging, when these sugars are lost, and positively, when they are restored. This opens an entirely new avenue for treating brain aging and related diseases.”

Bertozzi highlights the importance of this breakthrough:

“This huge structural change in the glycocalyx was hiding in plain sight because no one had thought to look at it before, or had the tools to do so.”

Implications for Alzheimer’s and Other Diseases

The study raises important questions about how the glycocalyx changes with age and whether similar processes occur in humans. Understanding these mechanisms could lead to new treatments for brain disorders like Alzheimer’s.

Shi, who is starting her own lab at Harvard University’s Rowland Institute, plans to expand this research to further investigate sugar molecules in neurodegeneration.

Could This Research Improve Drug Delivery to the Brain?

Beyond aging and disease, this discovery could also impact drug development. The blood-brain barrier makes it difficult for medicines to reach the brain, limiting treatment options for conditions like multiple sclerosis and brain cancer.

By understanding how the glycocalyx affects the brain’s defenses, scientists might develop new strategies to deliver drugs more effectively.

For now, this study represents a first step into an unexplored area of brain science. Shi is eager to continue unlocking the mysteries of the glycocalyx and finding ways to protect and restore brain health.

As she puts it:

“I’m excited to unlock the secrets of the glycocalyx in brain aging and neurodegeneration and discover how we can harness its potential to improve brain health.”

This discovery reshapes our understanding of brain aging and could pave the way for new treatments to slow cognitive decline and improve quality of life for aging individuals.

If you care about dementia, please read studies that eating apples and tea could keep dementia at bay, and Olive oil: a daily dose for better brain health.

For more health information, please see recent studies what you eat together may affect your dementia risk, and time-restricted eating: a simple way to fight aging and cancer.

The research findings can be found in Nature.

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