# GPR12 as a Novel Regulator of APP Expression: Relevance to Epilepsy and Alzheimer’s Disease

> **NIH NIH R21** · EMORY UNIVERSITY · 2020 · $429,002

## Abstract

Project Summary
 A significant fraction of epilepsy patients cannot be effectively treated by current medications. For this
reason, new drug targets that can modulate seizure vulnerability are needed. G protein-coupled receptors
(GPCRs) are outstanding drugs targets, and thus GPCRs that can influence seizure vulnerability are of special
interest to study as potential new drug targets in the treatment of epilepsy. The GPCR known as GPR12 has
been linked in genetic studies to epilepsy in humans. Moreover, recent data from our lab has shown that
GPR12 forms a complex with the amyloid precursor protein (APP) and exerts striking control over APP
expression in cultured cells. These two observations are potentially linked, as APP is known to strongly
influence seizure vulnerability in vivo. We hypothesize that GPR12 regulates APP processing via physical
association and/or receptor signaling, with this regulation contributing to GPR12 modulation of seizure
vulnerability. These ideas will be tested in two aims: i) we will dissect the interaction between GPR12 and
APP and determine how GPR12 controls APP expression, and ii) we will examine GPR12-mediated regulation
of APP in vivo and also assess GPR12 modulation of seizure vulnerability in a mouse model. If deletion of
GPR12 is found to result in both perturbed APP levels in vivo and altered seizure vulnerability, these findings
would set the stage for future studies focused on determining how these two observations might be related.
Moreover, such findings would also pave the way for the eventual targeting of GPR12 by drug-like small
molecules to develop novel therapeutics for the treatment of epilepsy and other disorders.
!

## Key facts

- **NIH application ID:** 9956908
- **Project number:** 1R21NS116318-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Randy A. Hall
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $429,002
- **Award type:** 1
- **Project period:** 2020-05-01 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9956908

## Citation

> US National Institutes of Health, RePORTER application 9956908, GPR12 as a Novel Regulator of APP Expression: Relevance to Epilepsy and Alzheimer’s Disease (1R21NS116318-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9956908. Licensed CC0.

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