# Structural and functional studies of the TRPM2 channel

> **NIH NIH R01** · VAN ANDEL RESEARCH INSTITUTE · 2022 · $475,000

## Abstract

ABSTRACT
Alzheimer’s disease (AD) is a devastating and incurable disease afflicting over millions of people worldwide. Its
pathogenesis is widely believed to be driven by the production and deposition of the β-amyloid peptide (Aβ),
causing disturbances in synaptic activity and neuronal death. Multiple studies have provided strong evidence
relating these effects to increased oxidative stress and to calcium imbalance resulting from aberrant activity of
calcium-permeable cation channels. Transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable
nonselective cation channel most highly expressed in the CNS, has been implicated in Alzheimer’s disease via
both amyloid-induced and oxidative stress-induced toxicity. Therefore, the TRPM2 channel is a promising
therapeutic target for the neurovascular impairment associated with AD and related diseases.
My current R01 grant (R01NS111031) focuses on structural and functional studies of the TRPM2 channel to
reveal its basic gating mechanism using single-particle electron microscopy, x-ray crystallography, and patch-
clamp electrophysiology. The redox-sensitive TRPM2 channel has been proven to be activated by Aβ peptide
and oxidative stress, which results in cytosolic calcium overload and causes neuron death in AD. I propose to
study the relationship of TRPM2 activity with Aβ and oxidative stress in this Alzheimer’s-Focused
Administrative Supplement NOT-AG-21-018. We believe that TRPM2, an important but understudied target in
AD, fits perfectly into the category of the Alzheimer’s-Focused Administrative Supplement Fund which would
allow us to generate the preliminary datasets needed to propel this unorthodox, high-risk-high-reward research
program forward.

## Key facts

- **NIH application ID:** 10499339
- **Project number:** 3R01NS111031-04S1
- **Recipient organization:** VAN ANDEL RESEARCH INSTITUTE
- **Principal Investigator:** Juan Du
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $475,000
- **Award type:** 3
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499339

## Citation

> US National Institutes of Health, RePORTER application 10499339, Structural and functional studies of the TRPM2 channel (3R01NS111031-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499339. Licensed CC0.

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