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Research from the **Buck Institute for Research on Aging** highlights a significant breakthrough that could reshape treatment strategies for Alzheimer’s disease. The study reveals a previously underestimated role of glycogen, a stored form of sugar in brain cells, in protecting against neurodegenerative diseases. The findings suggest that glycogen may play a crucial role in combating the toxic protein accumulation associated with Alzheimer’s and other cognitive disorders.
According to **Pankaj Kapahi**, a professor and senior scientist at the Buck Institute, “Stored glycogen doesn’t just sit there in the brain; it is involved in pathology.” This perspective shifts the scientific community’s understanding of glycogen, previously dismissed as biologically insignificant due to its limited presence in the brain.
Discovering Glycogen’s Role in Neurodegeneration
The research team initially conducted experiments using fruit fly models of Alzheimer’s disease. They found that when tau proteins, a key contributor to neurodegeneration, accumulate in the brain, they trap glycogen, hindering its breakdown. This glycogen buildup not only contributes to further tau accumulation but also impairs neurons’ ability to manage oxidative stress, a major factor in brain cell damage.
Remarkably, the team validated their findings in human cell models. In neurons exhibiting tau buildup, similar patterns of glycogen entrapment and metabolic dysfunction were observed.
To mitigate this detrimental cycle, the researchers enhanced levels of an enzyme known as **glycogen phosphorylase (GlyP)**. This enzyme initiates the breakdown of glycogen, and when its activity increased, neurons regained their capacity to detoxify harmful molecules called reactive oxygen species. **Sudipta Bar**, the lead researcher, stated, “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.”
A New Target for Dementia Treatment
This research opens the door to a novel approach for treating dementia. Instead of directly targeting tau proteins, this method aims to help neurons maintain their metabolic balance. The implications of this could be profound, as it suggests that existing drugs could be repurposed to activate the brain’s own detoxification systems.
An intriguing aspect of the study is the potential connection between GlyP and **GLP-1 receptor agonist drugs**, which are widely used for weight loss and diabetes management. The researchers noted that GlyP levels can be naturally increased through fasting behaviors. Kapahi remarked, “This work could explain why GLP-1 drugs, now widely used for weight loss, show promise against dementia, potentially by mimicking dietary restriction.”
The study also indicated that human neurons from patients with **frontotemporal dementia (FTD)** responded positively to GlyP activation, suggesting that this strategy might benefit various forms of neurodegeneration.
The findings of this research, published in **Nature Metabolism**, suggest a shift in Alzheimer’s research focus towards supporting brain sugar metabolism rather than solely combating tau and amyloid plaques. Kapahi emphasized the significance of this discovery, stating, “By discovering how neurons manage sugar, we may have unearthed a novel therapeutic strategy: one that targets the cell’s inner chemistry to fight age-related decline.”
As the global population ages, insights like these provide hope for better understanding—and potentially rebalancing—our brain’s hidden sugar code, paving the way for effective tools against dementia.
