# Targeting the mitochondrial protein mitoNEET for the treatment of reperfusion-injury after stroke

> **NIH NIH P20** · WEST VIRGINIA UNIVERSITY · 2021 · $300,737

## Abstract

PROJECT SUMMARY
Stroke is the fifth leading cause of death and the leading cause of disability in the United States. There remains
a critical need for innovative therapeutic approaches that can successfully prevent or reverse brain injury
following stroke. Dysfunction of the mitochondrial biochemistry following ischemic stroke and reperfusion injury
contributes to significant neuronal cell loss; however, the development of therapeutics targeting mitochondrial
function for stroke patients are lacking. Mitochondrial dysfunction plays a central role in the neuronal cell death
seen in ischemia-reperfusion injury, but has not yet been fully investigated as drug target. In this project, we are
investigating novel mitochondrial protein mitoNEET as therapeutic drug target of mitochondrial function in stroke.
MitoNEET is a newly discovered protein that regulates mitochondrial bioenergetics. We developed a first-in-
class mitoNEET agonist NL-1 which showed significant tissue protection after transient ischemia in the brain.
The objectives of this proposal are to evaluate a recently discovered mitochondrial protein, mitoNEET, as an
effective therapeutic approach for the pharmacological treatment of stroke. MitoNEET (CISD1 gene) regulates
mitochondrial bioenergetics capacity where it functions as redox sensor. Our central hypothesize is that ligands
selectively binding to mitoNEET will protect brain tissue from hypoxia-induced reperfusion injury, by reducing
mitochondrial dysfunction and oxidative stress. In our first aim, we will determine the pharmacological effect of
the mitoNEET ligands in a mouse model of middle cerebral ischemic reperfusion injury, and evaluate the duration
of the therapeutic window of the mitoNEET agonists where compounds will still be effective in preventing
neuronal cell death if given after a reperfusion injury. In the second aim, we will develop potent and selective
mitoNEET ligands with blood-brain barrier permeability properties. Predicted outcomes are that mitoNEET
agonists will be neuroprotective in stroke. These findings will have far-reaching implication for developing
neuroprotective medications as a treatment strategy for limiting the mitochondrial contribution to cell loss in the
clinical setting in the treatment of stroke patients.

## Key facts

- **NIH application ID:** 10217166
- **Project number:** 5P20GM109098-07
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** Werner Geldenhuys
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $300,737
- **Award type:** 5
- **Project period:** 2014-09-08 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217166

## Citation

> US National Institutes of Health, RePORTER application 10217166, Targeting the mitochondrial protein mitoNEET for the treatment of reperfusion-injury after stroke (5P20GM109098-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10217166. Licensed CC0.

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