# RNA-Based Potentiatorsfor AMPA and Kainate Receptors

> **NIH NIH R56** · STATE UNIVERSITY OF NEW YORK AT ALBANY · 2020 · $542,849

## Abstract

AMPA and kainate receptors are different subtypes of the glutamate ion channel family. AMPA
receptors mediate the majority of excitatory neurotransmission in the brain, and they are
indispensable for brain activities such as memory and learning. Potentiation of AMPA receptors
has been shown in both animal and clinical studies to improve cognitive activities such as
memory. However, a lack of potent, subtype-selective and subunit-selective potentiators or
positive modulators of AMPA receptors has hindered the development of effective drugs for a
treatment of age-associated memory impairment and loss. Having subtype-selective potentiators
would give us the ability to augment only those AMPA receptor subunits that are involved in
memory deficits, but leave those uninvolved untouched. This is because the expression of AMPA
receptors and channels in the brain is age-, tissue- and disease-dependent. Therefore, any
desirable positive modulators as drug candidates should be highly selective to avoid off-target
effects. Our preliminary data have shown we have been able to develop AMPA receptor-selective
and separately kainate receptor-selective potentiating aptamers. No known kainate receptor
potentiating agent has ever been reported. Thus, the therapeutic utility of a kainate receptor
selective potentiator has not yet been explored. The hypothesis to be tested is that the use of a
combination of two approaches, i.e., systematic evolution of ligands by exponential enrichment
(SELEX) to evolve RNA aptamers from a RNA library, and a set of functional assays, including a
laser-pulse photolysis technique to characterize aptamers with the functional (i.e., non-desensitized) receptor forms in the microsecond-to-millisecond time domain, will enable us to
identify potent, subtype-selective potentiating RNA aptamers for both AMPA and kainate
receptors. The use of the SELEX approach to design and to discover AMPA receptor potentiators
represents a paradigm shift from conventional potentiator/drug development strategies. RNA
potentiating aptamers themselves represent a new class of positive modulators with a high
potential as both tool molecules for neuroscience research and drug candidates for a potential
therapy for cognitive impairment in aging.

## Key facts

- **NIH application ID:** 10231300
- **Project number:** 1R56AG066015-01A1
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT ALBANY
- **Principal Investigator:** LI NIU
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $542,849
- **Award type:** 1
- **Project period:** 2020-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231300

## Citation

> US National Institutes of Health, RePORTER application 10231300, RNA-Based Potentiatorsfor AMPA and Kainate Receptors (1R56AG066015-01A1). Retrieved via AI Analytics 2026-06-26 from https://api.ai-analytics.org/grant/nih/10231300. Licensed CC0.

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