# The role of cholesterol metabolic enzyme CYP46A1 and its metabolite 24S-hydroxycholesterol in ischemic stroke.

> **NIH NIH R01** · MOREHOUSE SCHOOL OF MEDICINE · 2022 · $355,000

## Abstract

PROJECT SUMMARY
The overall objectives for this application are to determine the role of cholesterol metabolic
enzyme CYP46A1 and its metabolite 24S-hydroxycholesterol (24S-HC) in ischemic stroke. Our
central hypothesis is that activation of CYP46A1 results in increased production of 24S-HC,
which contributes to ischemic brain injury through potentiation of NMDAR. To test our
hypothesis, we will use a combination of in vitro and in vivo stroke models along with
electrophysiology, calcium imaging and transgenic mice to pursue the following three specific
aims: Aim 1. Determine the role of CYP46A1 in ischemic brain injury; Aim 2. Determine the role
and molecular mechanism of 24S-HC in ischemic neuronal injury in vitro; Aim 3. Define the
signaling cascade underlying the role of CYP46A1 in ischemic brain injury. Success of the
proposed research will define the role of cholesterol metabolic enzyme CYP46A1 and its
metabolite 24S-HC in ischemic brain injury.

## Key facts

- **NIH application ID:** 10503336
- **Project number:** 1R01NS128018-01
- **Recipient organization:** MOREHOUSE SCHOOL OF MEDICINE
- **Principal Investigator:** TIANDONG LENG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $355,000
- **Award type:** 1
- **Project period:** 2022-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10503336

## Citation

> US National Institutes of Health, RePORTER application 10503336, The role of cholesterol metabolic enzyme CYP46A1 and its metabolite 24S-hydroxycholesterol in ischemic stroke. (1R01NS128018-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10503336. Licensed CC0.

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