# FOXOs in ischemic stroke

> **NIH NIH R01** · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · 2024 · $371,025

## Abstract

PROJECT SUMMARY
Cerebral ischemia-reperfusion (I/R) is associated with neuroinflammation, mitochondrial dysfunction and
oxidative stress, leading to brain injury, function disability and development of Alzheimer’s disease-like
pathology and dementia. To fight against I/R induced pathological cascades, numerous neuroprotective
strategies and reagents have been identified and studied. However, translation of these neuroprotective
strategies and reagents to clinical trials has been unsuccessful, and to date, the tissue plasminogen activator
remains to be the only FDA approved drug for treating ischemic stroke. Thus, it is obligatory to identify and
validate additional therapeutic targets and reagents for I/R-caused brain disorder. The objective of this project
is to validate a novel therapeutic target, FOXO4, as previous data have shown that FOXO4 promotes early
tissue inflammation, and downregulation of FOXO4 is associated with reduced cell death and increased
neovasculature in ischemic peripheral tissues. Importantly, our pilot data have shown that knockout (KO) of
FOXO4 gene dramatically attenuates I/R-caused brain injury and alters numerous genes linked to AD in an
ischemic stroke mouse model. Based on these observations, we hypothesize that selective inhibition of
FOXO4 activity is protective against ischemic stroke-caused brain injury and AD-like pathology. To test the
hypothesis, we will (1) determine the role of FOXO4 in ischemic stroke-induced brain injury using genetically
modified mice, (2) study the role of identified FOXO4 inhibitors in treating ischemic stroke-caused brain injury,
and (3) understand how loss of FOXO4 confers neuroprotection following ischemic stroke.

## Key facts

- **NIH application ID:** 11052785
- **Project number:** 7R01NS124846-03
- **Recipient organization:** TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
- **Principal Investigator:** Hongmin Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $371,025
- **Award type:** 7
- **Project period:** 2024-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11052785

## Citation

> US National Institutes of Health, RePORTER application 11052785, FOXOs in ischemic stroke (7R01NS124846-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11052785. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*