# Brain Glycogen - Metabolism, Mechanisms, and Therapeutic Potential

> **NIH NIH R35** · UNIVERSITY OF KENTUCKY · 2021 · $1,945

## Abstract

Brain metabolism is a fundamental aspect of biology and human disease. The brain critically depends on
glucose, consuming large quantities as the biochemical fuel for cognition, memory, and behavior. Fundamental
aspects of brain metabolism have been extensively studied, but recent evidence regarding the key role of
glucose and glycogen metabolism in neurological diseases has recently opened up new avenues of research.
The neurological disease where aberrant glucose metabolism has been investigated in-depth is Lafora disease
(LD). LD is an autosomal recessive, fatal, glycogen storage disease (GSD) that equally affects both sexes.
Symptoms emerge in adolescence with drug-resistant epilepsy, ataxia, neurodegeneration, and a rapid decline
into a vegetative state before death. Results from several labs using multiple models have demonstrated that
aberrant intracellular glycogen-like aggregates, known as polyglucosan bodies (PGBs), are the cause of LD.
Strikingly, we and others have identified PGBs in multiple neurological diseases and we hypothesize that
PGBs are a driving force in disease progression for brain-impacted GSDs, and that PGBs also play a
critical role in Alzheimer's disease (AD).
 We have made foundational discoveries regarding glucose hypometabolism in LD, defined how PGBs
impact cellular processes, developed cutting-edge tools to determine the underlying cellular mechanisms, and
established therapeutic platforms to inhibit and/or eliminate PGBs. Defining the mechanisms of glycogen
metabolism in LD provides insights into how PGBs form and impact brain homeostasis. Thus, LD offers a
unique window into both normal brain glucose metabolism and broader disease implications when this
metabolism is perturbed.
 This supplement will allow Mr. Trey Coburn to further hone his skills in neuroscience. His results will assist
in determining the role of PGBs in AD. He will look at perturbations in signaling at the molecular level,
elucidate changes in cellular physiology, and establish novel therapeutic modalities at the organismal level.

## Key facts

- **NIH application ID:** 10285469
- **Project number:** 3R35NS116824-01S1
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Matthew S. Gentry
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,945
- **Award type:** 3
- **Project period:** 2021-03-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10285469

## Citation

> US National Institutes of Health, RePORTER application 10285469, Brain Glycogen - Metabolism, Mechanisms, and Therapeutic Potential (3R35NS116824-01S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10285469. Licensed CC0.

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