Pituitary Adenylate Cyclase Activating Polypeptide (PACAP)

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved neuropeptide belonging to the vasoactive intestinal peptide (VIP)/secretin/glucagon family. It exists primarily in two biologically active forms: PACAP38 and PACAP27. PACAP exerts its effects through three main G protein-coupled receptors: PAC1, VPAC1, and VPAC2. It is widely distributed throughout the central nervous system and peripheral organs, playing regulatory roles and exerting cytoprotective effects. Altered expression or function of PACAP or its receptors has been implicated in several conditions including migraine, PTSD, inflammatory diseases within the GI tract, neuronal injury responses, diabetes complications, neoplastic processes, alcohol use disorders, learning/memory deficits, and circadian rhythm disturbances. Targeted therapies using monoclonal antibodies against either PACAP itself or its primary receptor (PAC1-R) are under investigation for headache disorders.

Monoclonal antibodies targeting PACAP or its primary receptor (PAC1-R) are under investigation.