# Precision Targeting of Heteromeric NMDA Receptors in Age-Related Memory Disorders

> **NIH NIH P20** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2022 · $207,370

## Abstract

The senior citizen population in the United States is growing, so new therapeutics to treat age-related 
memory loss are needed to protect personal independence and reduce the burden of Alzheimer’s disease 
(AD). Ionotropic glutamate receptors of the NMDA subtype (NMDARs) are necessary for normal learning 
and memory, but NMDAR-targeting therapeutics are minimally effective in lessening the severity of AD 
symptoms and are not approved to treat memory loss in non-pathological brain aging. NMDARs are 
biochemically diverse tetramers formed between GluN1 and GluN2 subunits. GluN2A and GluN2B isoforms 
are abundantly expressed in the hippocampus, but selective ligands that target GluN2A or GluN2B have 
produced conflicting accounts of NMDAR contribution to memory and neural functions over the lifespan. 
Unexplored are contributions of tri-heteromeric NMDARs that contain GluN1, GluN2A and GluN2B. This 
project will innovate the scientific study of NMDARs by developing new ligands that are selective for the 
GluN1/GluN2A/GluN2B tri-heteromeric NMDAR and investigate how naturally occurring and experimentally 
induced changes in GluN2 isoforms regulate formation of tri-heteromers in the aging brain. These studies 
will be significant because they will create new tools to target a broader range of naturally occurring 
heteromeric NMDARs and identify how interactions between GluN2 isoforms influence neural function in 
brain aging. Ultimately, these discoveries will open new avenues to develop NMDAR-targeting therapeutics 
that are effective in preventing or reversing memory loss that emerges in advanced aging.

## Key facts

- **NIH application ID:** 10624058
- **Project number:** 5P20GM109091-09
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Joseph Aloysius McQuail
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $207,370
- **Award type:** 5
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10624058

## Citation

> US National Institutes of Health, RePORTER application 10624058, Precision Targeting of Heteromeric NMDA Receptors in Age-Related Memory Disorders (5P20GM109091-09). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10624058. Licensed CC0.

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