Estrogen Regulation of Cholesterol Metabolism During Myelin Damage and Repair
Principal Investigator
Meredith Hartley, Assistant Professor of Chemistry
Issue
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 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.
Response
Addressing significant questions in women’s health at the intersection of hormone regulation and neurological health, this project aims to define how CNS lipids are regulated by estrogen and how this affects neurological disease. Research Project Leader Meredith Hartley and her team employ an interdisciplinary approach in determining how estrogen regulates myelin and myelin lipid components during demyelination and remyelination.
Project Details
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 the regulation of cholesterol synthesis and recycling.
The central hypothesis will be evaluated by two specific aims:
- Define how estrogen signaling modulates myelin repair
- Map how estrogen signaling affects CNS cholesterol metabolites during myelin damage and repair
Completion of the proposed research will reveal mechanistic insights into how estrogen regulates cholesterol metabolism during CNS demyelination and remyelination. Revealing the way in which estrogen controls CNS cholesterol during neurological disease may provide insight into why women experience cognitive decline during menopause and more severe neurological symptoms in CNS diseases after menopause. Insights may aid the development of pro-remyelination agents that would have clinical benefits in CNS diseases with myelin damage.