Revealing Melatonin’s Mysteries: Receptors, signaling pathways, and
therapeutics applications
Abstract
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.