{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T09:11:30Z","timestamp":1778404290437,"version":"3.51.4"},"reference-count":328,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T00:00:00Z","timestamp":1568764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Emerging from the depths of evolution, pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors (i.e., PAC1, VPAC1, VPAC2) are present in multicellular organisms from Tunicates to humans and govern a remarkable number of physiological processes. Consequently, the clinical relevance of PACAP systems spans a multifaceted palette that includes more than 40 disorders. We aimed to present the versatility of PACAP1-38 actions with a focus on three aspects: (1) when PACAP1-38 could be a cause of a malfunction, (2) when PACAP1-38 could be the cure for a malfunction, and (3) when PACAP1-38 could either improve or impair biology. PACAP1-38 is implicated in the pathophysiology of migraine and post-traumatic stress disorder whereas an outstanding protective potential has been established in ischemia and in Alzheimer\u2019s disease. Lastly, PACAP receptors could mediate opposing effects both in cancers and in inflammation. In the light of the above, the duration and concentrations of PACAP agents must be carefully set at any application to avoid unwanted consequences. An enormous amount of data accumulated since its discovery (1989) and the first clinical trials are dated in 2017. Thus in the field of PACAP research: \u201cthis is not the end, not even the beginning of the end, but maybe the end of the beginning.\u201d<\/jats:p>","DOI":"10.3390\/jcm8091488","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T11:01:15Z","timestamp":1568804475000},"page":"1488","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Pituitary Adenylate Cyclase-Activating Polypeptide: 30 Years in Research Spotlight and 600 Million Years in Service"],"prefix":"10.3390","volume":"8","author":[{"given":"Viktoria","family":"Denes","sequence":"first","affiliation":[{"name":"Department of Experimental Zoology and Neurobiology, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Geck","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Tufts University, Boston, MA 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrienn","family":"Mester","sequence":"additional","affiliation":[{"name":"Department of Experimental Zoology and Neurobiology, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Gabriel","sequence":"additional","affiliation":[{"name":"Department of Experimental Zoology and Neurobiology, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/0006-291X(89)91757-9","article-title":"Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells","volume":"164","author":"Miyata","year":"1989","journal-title":"Biochem. 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