Calcitonin Gene-Related Peptide (CGRP)
A 37 amino acid neuropeptide produced by alternative splicing of the calcitonin gene, widely distributed in the central and peripheral nervous systems. CGRP is a potent vasodilator and plays a key role in migraine pathophysiology. CGRP-targeting therapies (primarily monoclonal antibodies) represent a major advance in migraine treatment.
Technical Context
CGRP (37 aa) is produced by alternative splicing of the CALCA gene — in C-cells, the gene produces calcitonin; in sensory neurons, it produces CGRP (alpha-CGRP). A related peptide (beta-CGRP) is encoded by the CALCB gene. CGRP is one of the most potent vasodilators known and is released from trigeminal sensory neurons during migraine attacks. It acts through a heterodimeric receptor complex of CLR (calcitonin receptor-like receptor) and RAMP1 (receptor activity-modifying protein 1). Anti-CGRP therapies (monoclonal antibodies erenumab, fremanezumab, galcanezumab; small molecule antagonists) have transformed migraine prevention. While these are primarily antibody-based rather than peptide drugs, understanding CGRP biology provides context for peptide signalling in neurovascular regulation.