TY - JOUR
T1 - Calcitonin/PAC1 receptor splice variants: a blind spot in migraine research
AU - Rees, Tayla A.
AU - Labastida-Ramírez, Alejandro
AU - Rubio-Beltrán, Eloisa
N1 - Funding Information:
The authors acknowledge Erica Hendrikse for generously proofreading the manuscript. T.A.R. acknowledges the support of the National Institute of Neurological Disorders and Stroke of the National Institutes of Health, United States under Award Number RF1NS113839 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health of the US Government. E.R-B. was the recipient of an Independent Research Award by the Institute of Psychiatry, Psychology, and Neuroscience, King’s College London .
Funding Information:
The authors acknowledge Erica Hendrikse for generously proofreading the manuscript. T.A.R. acknowledges the support of the National Institute of Neurological Disorders and Stroke of the National Institutes of Health, United States under Award Number RF1NS113839. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health of the US Government. E.R-B. was the recipient of an Independent Research Award by the Institute of Psychiatry, Psychology, and Neuroscience, King's College London. All authors declare no conflict of interest.
Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/10
Y1 - 2023/10
N2 - The neuropeptides calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) and their receptors are linked to migraine neurobiology. Recent antimigraine therapeutics targeting the signaling of these neuropeptides are effective; however, some patients respond suboptimally, indicating an incomplete understanding of migraine pathophysiology. The CGRP- and PACAP-responsive receptors can be differentially spliced. It is known that receptor splice variants can have different pathophysiological effects in other receptor-mediated pain pathways. Despite considerable knowledge on the structural and pharmacological differences of the CGRP- and PACAP-responsive receptor splice variants and their expression in migraine-relevant tissues, their role in migraine is rarely considered. Here we shine a spotlight on the calcitonin and PACAP (PAC1) receptor splice variants and examine what implications they may have for drug activity and design.
AB - The neuropeptides calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) and their receptors are linked to migraine neurobiology. Recent antimigraine therapeutics targeting the signaling of these neuropeptides are effective; however, some patients respond suboptimally, indicating an incomplete understanding of migraine pathophysiology. The CGRP- and PACAP-responsive receptors can be differentially spliced. It is known that receptor splice variants can have different pathophysiological effects in other receptor-mediated pain pathways. Despite considerable knowledge on the structural and pharmacological differences of the CGRP- and PACAP-responsive receptor splice variants and their expression in migraine-relevant tissues, their role in migraine is rarely considered. Here we shine a spotlight on the calcitonin and PACAP (PAC1) receptor splice variants and examine what implications they may have for drug activity and design.
UR - http://www.scopus.com/inward/record.url?scp=85166617256&partnerID=8YFLogxK
U2 - 10.1016/j.tips.2023.07.003
DO - 10.1016/j.tips.2023.07.003
M3 - Review article
SN - 0165-6147
VL - 44
SP - 651
EP - 663
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
IS - 10
ER -