# Metabolic Master Regulators for Ischemic Neuroprotection

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $373,174

## Abstract

Project Summary
Cerebral ischemia as a result of strokes or cardiac arrest remains one of the leading causes of death and
disability in the U.S.A. It is now well accepted that mitochondria are key players in cerebral
ischemic/reperfusion injury hours to days following the ischemic insult. The main goals were the elucidation of
signaling pathways involved in the fate of brain mitochondria following cerebral ischemia. Studies from us and
other groups, have demonstrated Protein Kinase C isozyme (PKCϵ) translocates to mitochondria to activate
pathways of neuroprotection. We have identified that PKCϵ acts as a signaling metabolic master regulator
that alters NAD levels, mitochondrial sirtuins and cell metabolism and promotes neuroprotection against
cerebral ischemia. Previous studies demonstrated the importance of NAD replenishment in neuroprotection
against cerebral ischemia. Thus, we propose experiments to elucidate the mechanisms by which PKCϵ alters
NAD levels in the brain and define its downstream pathways that enhance ischemic tolerance. These goals will
be achieved in the following specific aims:
1) To determine if PKCε via Sirt1 promotes increases of the NAD+ biosynthetic pathway and define the role of
this pathway in ischemic neuroprotection. Model: Mouse; Paradigm: Oxygen-Glucose Deprivation (OGD); 2)
To determine if the PKCε/Sirt1 pathway promotes a `caloric restriction' (CR)-like bioenergetic phenotype in the
brain. Model: Mouse; Paradigm: Oxygen-Glucose Deprivation (OGD), Middle Cerebral Artery Occlusion
(MCAo); and 3) To determine whether post-treatment with a PKCε activator can rescue the NAD+ salvage
pathway and its downstream pathways following MCAo in aged rats. Model: Rat; Paradigm: MCAo.

## Key facts

- **NIH application ID:** 10216751
- **Project number:** 3R01NS097658-04S1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** MIGUEL A PEREZ-PINZON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $373,174
- **Award type:** 3
- **Project period:** 2017-08-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216751

## Citation

> US National Institutes of Health, RePORTER application 10216751, Metabolic Master Regulators for Ischemic Neuroprotection (3R01NS097658-04S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10216751. Licensed CC0.

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