Calcitonin gene-related peptide alpha (CGRP (α-CGRP))

Calcitonin gene-related peptide alpha (α-CGRP), encoded by the CALCA gene, is a 37-amino acid neuropeptide resulting from alternative splicing of the calcitonin/CGRP gene on chromosome 11[1][2][4]. α-CGRP is primarily expressed in sensory neurons and serves as a potent vasodilator, neuromodulator, and neurotransmitter, where it plays a prominent role in regulating vascular tone, pain transmission (notably in migraine), and inflammatory processes[1][3][4]. CALCA also encodes other bioactive peptides—calcitonin (regulates calcium and phosphate homeostasis) and katacalcin (a calcium-lowering peptide)[2]. α-CGRP mediates its effects via the heteromeric CGRP receptor complex, which consists of the calcitonin receptor-like receptor (CALCRL) and receptor activity-modifying protein 1 (RAMP1), a member of the secretin-like family of G protein-coupled receptors[3][4]. Elevated CGRP levels are associated with migraines and other pain syndromes, and the CGRP pathway is an important target for new therapeutic agents in migraine management[2][3][4].

Other names

Calcitonin related polypeptide alphaCALCACalcitoninKatacalcinCALC1CTCCPCalcitonin gene-related peptide 1CGRP1CGRP-ICGRPCGRP-alphaAlpha-type CGRPCalcitonin gene-related peptide ICalcitonin carboxyl-terminal peptidePDN-21KCPCT

Monoclonal antibodies that bind and neutralize CGRP or block its receptor, preventing activation (e.g., erenumab, fremanezumab, galcanezumab, eptinezumab) Small-molecule antagonists (gepants, e.g., telcagepant, rimegepant, ubrogepant) block the CGRP receptor and inhibit its downstream signaling