Small Molecule Inhibition of ERK Signaling at the PAC1 Receptor

Presenter's Name(s)

Waverly Gebhardt

Conference Year

2023

Abstract

The Pac1 receptor is a GPCR preferentially activated by PACAP. When PACAP signaling is hyperactive its becomes maladaptive in the form of chronic pain and stress disorders. The Pac1 receptor is tied to Gαq and Gαs pathways and exhibits β-arrestin mediated endosomal ERK signaling. This ERK signaling is necessary for the maladaptive PACAP-Pac1 response. The goal of the study was to target the ERK signaling without effecting the homeostatic signaling. Western blots were used to quantitate the effect of various small molecules on Pac1 ERK signaling. The data show that several small molecules were able to block the ERK signaling.

Primary Faculty Mentor Name

Victor May

Status

Undergraduate

Student College

College of Arts and Sciences

Program/Major

Neuroscience

Primary Research Category

Life Sciences

Abstract only.

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Small Molecule Inhibition of ERK Signaling at the PAC1 Receptor

The Pac1 receptor is a GPCR preferentially activated by PACAP. When PACAP signaling is hyperactive its becomes maladaptive in the form of chronic pain and stress disorders. The Pac1 receptor is tied to Gαq and Gαs pathways and exhibits β-arrestin mediated endosomal ERK signaling. This ERK signaling is necessary for the maladaptive PACAP-Pac1 response. The goal of the study was to target the ERK signaling without effecting the homeostatic signaling. Western blots were used to quantitate the effect of various small molecules on Pac1 ERK signaling. The data show that several small molecules were able to block the ERK signaling.