{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:46:37Z","timestamp":1790217997260,"version":"4.1.0"},"reference-count":99,"publisher":"Georg Thieme Verlag KG","issue":"06","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Melatonin (5-methoxy-acetyl tryptamine) is a sleep-inducing hormone, and the\n                    pineal gland produces it in response to the circadian clock of darkness. In the\n                    body, MT1 and MT2 receptors are mostly found, having an orthosteric pocket and\n                    ligand binding determinants. Melatonin acts by binding on melatonin receptors,\n                    intracellular proteins, and orphan nuclear receptors. It inhibits adenyl cyclase\n                    and activates phospholipase C, resulting in gene expression and an intracellular\n                    alteration environment. Melatonin signaling pathways are also associated with\n                    other intracellular signaling pathways, i.\u2009e., cAMP\/PKA and\n                    MAPK\/ERK pathways. Relative expression of different proteins depends on\n                    the coupling profile of G protein, accounting pharmacology of the melatonin\n                    receptor bias system, and mediates action in a Gi-dependent manner. It shows\n                    antioxidant, antitumor, antiproliferative, and neuroprotective activity.\n                    Different types of melatonin agonists have been synthesized for the treatment of\n                    sleeping disorders. Researchers have developed therapeutics that target\n                    melatonin signaling, which could benefit a wide range of medical conditions.\n                    This review focuses on melatonin receptors, pharmacology, and signaling\n                    cascades; it aims to provide basic mechanical aspects of the receptor\u2019s\n                    pharmacology, melatonin\u2019s functions in cancer and neurodegenerative\n                    diseases, and any treatments and drugs designed for these diseases. This will\n                    allow a basic comparison between the receptors in question, highlighting any\n                    parallels and differences that may exist and providing fundamental knowledge\n                    about these receptors to future researchers.<\/jats:p>","DOI":"10.1055\/a-2226-3971","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T19:06:57Z","timestamp":1702321617000},"page":"405-418","source":"Crossref","is-referenced-by-count":16,"title":["Revealing Melatonin\u2019s Mysteries: Receptors, Signaling\n                    Pathways, and Therapeutics Applications"],"prefix":"10.1055","volume":"56","author":[{"given":"Kulsoom","family":"Kulsoom","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Bahauddin Zakariya University, Multan,\n                    Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5716-0597","authenticated-orcid":false,"given":"Wajahat","family":"Ali","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xi\u2019an Jiaotong University,\n                    Xian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainab","family":"Saba","sequence":"additional","affiliation":[{"name":"Department of Optometry, Khwaja Fareed University of Engineering\n                    & Information Technology, Rahim Yar Khan, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabab","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental\n                    Sciences, Universita degli studi di Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samra","family":"Zahra","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University Islamabad,\n                    Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Irshad","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, University of\n                    Trieste, Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Saeed","family":"Ramzan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, The Islamia University of Bahawalpur,\n                    Bahawalpur, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,2,19]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"472","DOI":"10.20945\/2359-3997000000066","article-title":"A brief review about melatonin, a pineal hormone","volume":"62","author":"F G do Amaral","year":"2018","journal-title":"Arch Endocrinol Metab"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41573-020-00109-w","article-title":"Circadian rhythm as a therapeutic target","volume":"20","author":"W Ruan","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.mito.2015.02.003","article-title":"Melatonin promotes Bax sequestration to mitochondria reducing cell\n                    susceptibility to apoptosis via the lipoxygenase metabolite\n                    5-hydroxyeicosatetraenoic acid","volume":"21","author":"F Radogna","year":"2015","journal-title":"Mitochondrion"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"471","DOI":"10.3390\/ijms23010471","article-title":"Membrane melatonin receptors activated cell signaling in physiology and\n                    disease","volume":"23","author":"G Nikolaev","year":"2021","journal-title":"Int J Mol Sci"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.sleep.2018.12.026","article-title":"Distal skin vasodilation in sleep preparedness, and its impact on thermal status\n                    in preterm neonates","volume":"60","author":"V Bach","year":"2019","journal-title":"Sleep Med"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"11208","DOI":"10.3390\/ijms140611208","article-title":"Melatonin receptor genes in vertebrates","volume":"14","author":"D Li","year":"2013","journal-title":"Int J Mol Sci"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"101974","DOI":"10.1016\/j.npep.2019.101974","article-title":"Cellular localization of melatonin receptor Mel1b in pigeon retina","volume":"78","author":"W Sheng","year":"2019","journal-title":"Neuropeptides"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1124\/pr.110.002832","article-title":"International Union of Basic and Clinical Pharmacology. 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