Alpha-calcitonin gene-related peptide (α-CGRP)

Alpha-calcitonin gene-related peptide (α-CGRP) is a 37-amino acid neuropeptide (UniProt P06881) and one of the most potent vasodilators in the human body (PubMed: 35222088). It is primarily synthesized in the cell bodies of the dorsal root and trigeminal ganglia and is released from sensory nerve endings to regulate vascular tone and pain signaling. α-CGRP plays a central role in the pathophysiology of migraine by mediating neurogenic inflammation and the transmission of pain signals within the trigeminovascular system (PubMed: 30248435). Beyond its role in pain, it exerts protective effects in the cardiovascular system by regulating blood pressure and protecting against ischemic injury (PubMed: 35222088). Therapeutic interventions targeting the CGRP pathway have revolutionized migraine treatment, including monoclonal antibodies that bind directly to the α-CGRP peptide (e.g., fremanezumab, galcanezumab) and those that block its receptor (e.g., erenumab). Additionally, small-molecule CGRP receptor antagonists, known as gepants, are used for both the acute and preventive treatment of migraine (StatPearls: NBK553131).

Other names

CGRPCGRP1Calcitonin gene-related peptide 1h-α-CGRPCALC1CGRP-alpha

Monoclonal antibody binding and sequestration of the CGRP ligand to prevent its interaction with the CGRP receptor complex (CLR/RAMP1), thereby inhibiting downstream adenylyl cyclase activation and cAMP production.