Sexual dimorphism of G protein-coupled receptor signaling in the brain

Abstract

G protein-coupled receptors (GPCRs) represent the most substantial family of membrane receptors that are targeted by U.S. Food and Drug Administration-approved drugs. Much of the preclinical research to understand the pharmacology of many membrane receptors including GPCRs is derived from studies in male animal models (Karp and Reavey, 2019). This can be of concern as emerging evidence reveals unexpected sex-dependent differences in GPCR pharmacodynamics. Thus, understanding the sex-specific disparities in GPCR pharmacological fingerprints can aid in developing targeted ligands that precisely correct GPCR signaling modalities in men and women and ultimately, enhance their effectiveness for certain pathophysiological conditions. We will attempt to summarize the current evidence supporting the sex-biased signaling of GPCRs implicated in several brain disorders.

Keywords G protein, Alzheimer's disease, Pathophysiological, sex-biased signaling