Neurons burn sugar differently: Discovery offers new hope for fighting neurodegeneration (Calorie restriction helps)

Medical Xpress / Buck Institute for Research on Aging / Nature Metabolism ^ | June 30, 2025 | Pankaj Kapahi, Ph.D. et al

[ConservativeMind]

A new study has revealed a surprising player in the battle against Alzheimer's disease and other forms of dementia: brain sugar metabolism. The research uncovers how breaking down glycogen—a stored form of glucose—in neurons may protect the brain from toxic protein buildup and degeneration.

The research team 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 buildup appears to contribute to disease progression. Bar says tau, the infamous 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)—which kicks off the process of glycogen breakdown—the researchers found they could reduce tau-related damage in fruit flies and human stem cell-derived neurons.

Rather than using glycogen as a fuel for energy production, these enzyme-supported neurons rerouted the sugar molecules into the pentose phosphate pathway (PPP)—a critical route for generating NADPH (nicotinamide adenine dinucleotide phosphate) and Glutathione, molecules that protect against oxidative stress.

"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 Bar.

Even more promising, the team demonstrated that dietary restriction (DR)—a well-known intervention to extend lifespan—naturally enhanced GlyP activity and improved tau-related outcomes in flies. They further mimicked these effects pharmacologically using a molecule called 8-Br-cAMP, showing that the benefits of DR might be reproduced through drug-based activation of this sugar-clearing system.

Researchers also confirmed similar glycogen accumulation and protective effects of GlyP in human neurons derived from patients with frontotemporal dementia (FTD).

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TOPICS: Health/Medicine
KEYWORDS: calorierestriction; calories; dementia; diet; neurons; sugar

[ConservativeMind]

Reducing calories and / or fasting improved the condition, resetting the stuck glycogen tied to tau protein:

“…the team demonstrated that dietary restriction (DR)—a well-known intervention to extend lifespan—naturally enhanced GlyP activity and improved tau-related outcomes…”

Dementia concerns might be backed off some this way, even if the condition already exists.

[ConservativeMind]

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[Veto!]

Of course.

I may be the only person in the world who hates sweet and salty foods. Don’t own a salt shaker. My idea of dessert is black raspberry yogurt from Trader Joe. May have a little sugar but tastes great. My fave flavor since I was 5 and Good Humor ice crveam drove up our road every couple of days

[blackdog]

You may not recognize your spouse, but you do recognize you’re starving hungry. That’s a success in medical terms.

[sauropod]

Bkmk

[sopo]

The new DR. Pepper may be for you. Comes in regular and zero sugar. They ran a commercial incessantly on that great All Star game last night. At least it was a cute one ( the commercial)