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Revealing Melatonin’s Mysteries: Receptors, signaling pathways, and therapeutics applications
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  • Kulsoom Kulsoom,
  • Wajahat Ali,
  • Zainab Saba,
  • Shabab Hussain,
  • Muhammad Yasin,
  • Samra Zahra,
  • Maria Irshad,
  • Muhammad Ramzan
Kulsoom Kulsoom
Bahauddin Zakariya University
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Wajahat Ali
Xi'an Jiaotong University School of Basic Medical Sciences

Corresponding Author:[email protected]

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Zainab Saba
Khwaja Fareed University of Engineering & Information Technology
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Shabab Hussain
University of Messina
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Muhammad Yasin
University of Baltistan
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Samra Zahra
COMSATS University Islamabad - Islamabad Campus
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Maria Irshad
University of Trieste
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Muhammad Ramzan
The Islamia University of Bahawalpur Pakistan
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Melatonin (5-methoxy-acetyl tryptamine) sleep-inducing hormone, and the pineal gland produces it in response to the circadian clock of darkness. In the body, MT1 and MT2 receptors are mostly found, having an orthosteric pocket and ligand binding determinants. Melatonin acts by binding on melatonin receptors, intracellular proteins, and orphan nuclear receptors. It inhibits adenyl cyclase and activates phospholipase C, resulting in gene expression and an intracellular alteration environment. Melatonin signaling pathways are also associated with other intracellular signaling pathways, i.e., cAMP/PKA and MAPK/ERK pathways. Relative expression of different proteins depends on the coupling profile of G protein, accounting pharmacology of the melatonin receptor bias system, and mediates action in a Gi-dependent manner. It shows antioxidant, antitumor, antiproliferative and neuroprotective activity. Different types of melatonin agonists have been synthesized for the treatment of sleeping disorders. Researchers have developed therapeutics that target melatonin signaling, which could benefit a wide range of medical conditions. This review focuses on melatonin receptors, pharmacology, and signaling cascades; it aims to provide basic mechanical aspects of the receptor’s pharmacology, melatonin functions in cancer and neurodegenerative diseases, and any treatments and drugs designed for these diseases. This will allow a basic comparison between the receptors in question, highlighting any parallels and differences that may exist and providing fundamental knowledge about these receptors to future researchers.