The therapeutic potential of melatonin: Focus on the SIRT1 signaling pathway

Melatonin (N-acetyl-5-methoxytryptamine) is a pleiotropic indoleamine involved in diverse physiological and cellular processes and has consequently been investigated in numerous disease models. This molecule is primarily produced in the pineal gland and is well-known for its diverse functions including antitumor, immunomodulatory, antioxidant, antihypertensive, and sedative effects. It is also involved in the regulation of body weight, gastrointestinal function, reproduction, thermoregulation, and cardioprotection. Melatonin exerts its protective effects by modulating various molecular pathways. Among the signaling pathways implicated in these effects, the sirtuin-1 (SIRT1) pathway has received considerable attention. SIRT1 is a well-studied member of the mammalian sirtuin family that functions as a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase. SIRT1 shuttles between the cytoplasm and the nucleus, where it deacetylates histones and other proteins. This activity impacts various cellular functions such as cell survival, metabolism, growth, aging, and stress resistance. Available evidence suggests that melatonin may modulate SIRT1 activity and thereby influence processes involved in inflammation, oxidative stress, apoptosis, and autophagy in various pathological conditions. However, evidence regarding the role of SIRT1 in the effects of melatonin remains limited In this review, we examine the pharmacological effects of melatonin across several disease models, with particular emphasis on the potential involvement of SIRT1 signaling.