Pituitární adenylátcyklázu aktivující polypeptid (PACAP) a jeho role v patofyziologii migrény

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Title in English	Pituitary adenylate cyclase activating polypeptide (PACAP) and its role in migraine pathophysiology
Authors	WEISS Viktor HARŠÁNY Michal ŘEHULKA Pavel
Year of publication	2023
Type	Article in Periodical
Magazine / Source	Ceska a slovenska neurologie a neurochirurgie
MU Faculty or unit	Faculty of Medicine
Citation
web	https://www.csnn.eu/en/journals/czech-and-slovak-neurology-and-neurosurgery/2023-3-9/pituitary-adenylate-cyclase-activating-polypeptide-pacap-and-its-role-in-migraine-pathophysiology-134903?hl=cs
Doi	http://dx.doi.org/10.48095/cccsnn2023177
Keywords	pituitary adenylate cyclase activating polypeptide; PACAP; cerebral blood flow; migraine; monoclonal antibodies
Description	During the three decades of studying vasoactive substances in migraine pathophysiology, ample theoretical knowledge has been accumulated that has ushered in a groundbreaking era in migraine treatment. Pituitary adenylate cyclase activating polypeptide (PACAP) is one of these promising therapeutic targets and the subject of ongoing clinical trials. In this review article, we focus on PACAP as an endogenous signaling molecule, describing its basic properties, binding to specific receptors (PAC1, VPAC1, VPAC2) and its bio logical activity. The latter relates to basic physiological processes of the organism (reproduction, nutrition, aging, etc.), neuroprotection in acute and chronic injury, and it is of particular importance in tissue and organ protection in ischemic stroke. The vasomotor eff ect of PACAP consists of cAMP-mediated relaxation of the cranial artery smooth muscle. In migraine patients, experimental application of PACAP induces vasodilation of the arteria meningea media and correlates with lateralized headache with a migrainous phenotype. Although this vasodilatation is preventable by sumatriptan, a monoclonal antibody directed against the PAC1 receptor (AMG301) completely failed in migraine prevention. Currently, the results of clinical trials (phase 1 and 2) of monoclonal antibodies directed against PACAP (ALD1910 or Lu-AG09222, LY3451838) are eagerly awaited. If their prophylactic effect in migraine is demonstrated, this would open a new therapeutic option for patients with previously failed treatment. However, a prerequisite for potential medical use will be the demonstration of long-term safety, especially with regard to cardiovascular health.