# Estrogen regulation of cholesterol metabolism during myelin damage and repair

> **NIH NIH P20** · UNIVERSITY OF KANSAS LAWRENCE · 2024 · $208,594

## Abstract

Project Summary
Women experience neurological diseases like multiple sclerosis and Alzheimer’s disease at a higher
prevalence than men, and disease symptoms increase in severity after menopause. These connections
suggest that there is a fundamental link between estrogen regulation and brain health. Myelin damage is a
feature common to both neurological disease states, however, there are no FDA-approved therapies that
directly target myelin repair. The long-term goal of this project is to define how CNS lipids are regulated by
estrogen and how this affects neurological disease. The overall objective in this application is to determine how
estrogen regulates myelin and myelin lipid components during demyelination and remyelination. Preliminary
data presented in the application reveals that cholesterol ester metabolism has dynamic changes in response
to myelin damage. Work from other groups demonstrated that estrogen can regulate genes related to
cholesterol metabolism during demyelination and remyelination. These data form the basis for the central
hypothesis that estrogen signaling maintains myelin and promotes remyelination in part through regulation of
cholesterol synthesis and recycling. The central hypothesis will be evaluated by two specific aims: (1) Define
how estrogen signaling modulates myelin repair; (2) Map how estrogen signaling affects CNS cholesterol
metabolites during myelin damage and repair. The proposed research is innovative, in the applicant’s opinion,
because it tackles significant questions in women’s health at the intersection of hormone regulation and
neurological disease using an interdisciplinary approach. The proposal also features a novel mouse model of
myelin repair developed by the applicant that enables the proposed experiments, which would not be possible
with other animal models. Completion of the proposed research will reveal mechanistic insights into how
estrogen regulates cholesterol metabolism during CNS demyelination and remyelination. This contribution is
expected to be significant because it will reveal how estrogen controls CNS cholesterol during neurological
disease and may provide insight into why women experience cognitive decline during menopause and more
severe neurological symptoms in CNS diseases after menopause. This will advance this area of women’s
health research by providing insights that may lead to the development of pro-remyelination agents that would
have clinical benefit in CNS diseases with myelin damage.

## Key facts

- **NIH application ID:** 10770246
- **Project number:** 1P20GM152280-01
- **Recipient organization:** UNIVERSITY OF KANSAS LAWRENCE
- **Principal Investigator:** Meredith D Hartley
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $208,594
- **Award type:** 1
- **Project period:** 2024-04-15 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10770246

## Citation

> US National Institutes of Health, RePORTER application 10770246, Estrogen regulation of cholesterol metabolism during myelin damage and repair (1P20GM152280-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10770246. Licensed CC0.

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