# Mechanisms of ASIC-mediated neuronal injury

> **NIH NIH R01** · MOREHOUSE SCHOOL OF MEDICINE · 2022 · $313,119

## Abstract

Abstract
 Ischemic stroke is a leading cause of death and long-term disability. Current drug
treatment is limited to tPA, which has a low success rate and potentially severe side effects.
Acidosis is a common feature of neurological disorders such as brain ischemia, and it has been
shown to play a critical role in stroke. The mechanisms, however, remained elusive. The
discovery that protons activate a distinct family of cation channels, the acid-sensing ion
channels (ASICs), has shed new light on acid-signaling and acidosis-mediated brain injury. The
studies in our laboratories in the past 10 years have provided convincing evidence suggesting
that activation of ASIC1a contributes markedly to acidosis-mediated ischemic brain injury.
Following our initial report, others have demonstrated an important role for ASIC1a activation in
spinal cord injury, traumatic brain injury, and axon degeneration. Thus, ASIC1a represents a
novel therapeutic target. Despite its well-established role in neurological disorders, the detailed
mechanisms underlying ASIC1a-mediated neuronal injury in stroke remain unclear. We now
have strong evidence suggesting that, besides the well-documented Ca2+ toxicity, a
combination of increased ASIC1a surface expression, Zn2+ toxicity, and an ion
conducting independent cell death pathway participate in ASIC-mediated neuronal
injury in ischemia. The objective of this application is to investigate the detailed molecular
mechanisms and pathways underlying ASIC-mediated neuronal injury. Given the limitations of
currently available pharmacological inhibitors that target these channels, e.g. the non-specificity
of amiloride and large molecule nature of PcTX1, the proposed studies may disclose novel and
alternative therapeutic strategies for ischemic brain injury.

## Key facts

- **NIH application ID:** 10440235
- **Project number:** 5R01NS104349-04
- **Recipient organization:** MOREHOUSE SCHOOL OF MEDICINE
- **Principal Investigator:** ROGER Pancoast SIMON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $313,119
- **Award type:** 5
- **Project period:** 2017-12-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440235

## Citation

> US National Institutes of Health, RePORTER application 10440235, Mechanisms of ASIC-mediated neuronal injury (5R01NS104349-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10440235. Licensed CC0.

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