323-Gq-Biased CCKBR Agonism for Alzheimer's Therapy

Paper Talk · Dec 18, 2025 · 13m

The article details a structural and pharmacological approach to treating Alzheimer’s disease (AD) by targeting the cholecystokinin B receptor (CCKBR), a G protein-coupled receptor crucial for memory and learning. The authors used cryo-electron microscopy to visualize the CCKBR complex bound to various G protein subtypes (Gq, Gs, and Gi), establishing that distinct receptor conformations are responsible for specific signal bias. This structural information enabled the rational design of synthetic small-molecule ligands, resulting in compounds like the exclusively Gi-biased agonist z-44 and…