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Melatonin: Physiological Effects on Health and Diseases
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Melatonin: Physiological Effects on Health and Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 674

Special Issue Editor

Dr. Jana Tchekalarova

E-Mail Website
Guest Editor
Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 23, 1113 Sofia, Bulgaria
Interests: neuroscience; neuropharmacology; antioxidants; neuroinflammation; models of neurodegenerative diseases; aging
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Melatonin is a hormone produced by the pineal gland in the brain that helps regulate the sleep–wake cycle. Its mechanism of action involves interaction with melatonin receptors in the brain, particularly in the suprachiasmatic nucleus, which is responsible for controlling the body’s circadian rhythm. By binding to these receptors, melatonin signals to the body that it is time to sleep, helping to promote relaxation and induce drowsiness.

In addition to its role in promoting sleep, melatonin also has antioxidant properties and plays a role in several physiological functions, including immune function and regulation of body temperature. Melatonin is a potent antioxidant via three approaches: direct scavenging of free radicals; stimulation of antioxidant enzymes; increasing the efficiency of mitochondrial oxidative phosphorylation and reducing electron leakage (thereby reducing free radical generation); and finally, it may potentiate other compounds with potential antioxidant activity.

Research has shown that melatonin may have potential benefits for several health conditions, including insomnia, jet lag, and certain mood disorders. It is also being studied for its potential role in conditions such as Alzheimer’s disease, cardiovascular disease, and certain types of cancer.

Understanding the underlying mechanisms involved in the beneficial effects of melatonin in physiological and pathogenic conditions contributes to the development of therapeutic strategies that target multiple diseases or pathways.

The current Special Issue invites the submission of research manuscripts, reviews, and short commentaries on topics related to the underlying mechanisms mediated by melatonin-related systems and the role of specific or general signaling involved in their activity. Submissions may include reports from animal models to clinical trials in the field of neurodegenerative diseases.

Dr. Jana Tchekalarova
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hormone melatonin
  • oxidative stress
  • sleep
  • metabolism
  • neurodegeneration

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Published Papers (2 papers)

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14 pages, 1169 KiB  
Article
The Novel Melatonin Analog Containing Donepezil Fragment Prevents Cognitive Impairments and Associated Oxidative Stress in a Hybrid Rat Model of Melatonin Deficiency and icvAβ1-42
by Petya Ivanova, Lidia Kortenska, Violina T. Angelova and Jana Tchekalarova
Int. J. Mol. Sci. 2025, 26(14), 6553; https://doi.org/10.3390/ijms26146553 - 8 Jul 2025
Viewed by 151
Abstract
Alzheimer’s disease (AD) is the most common cause of dementia in older adults and is becoming a major public health crisis as life expectancy increases worldwide. A major contributor to this disease is a deficiency in melatonin signaling. We have recently synthesised a [...] Read more.
Alzheimer’s disease (AD) is the most common cause of dementia in older adults and is becoming a major public health crisis as life expectancy increases worldwide. A major contributor to this disease is a deficiency in melatonin signaling. We have recently synthesised a series of melatonin analogs containing donepezil fragments. These compounds have been tested both in silico and in vitro. In this study, a particularly potent compound, 3a, was evaluated in a hybrid rat model of melatonin deficiency and AD. Rats underwent pinealectomy followed one week later by bilateral intracerebroventricular infusion of Aβ1-42 (1 µg/µL). A 14-day subchronic treatment with compound 3a was started simultaneously with the neurotoxin infusion. Melatonin was used as a reference drug, while a matched sham group received vehicle treatment. One week after the Aβ1-42 infusion, the rats’ cognitive functions were assessed using two Y-maze protocols, object recognition and object location tests. Markers of oxidative stress, including hippocampal glutathione, superoxide dismutase, and malondialdehyde, were assessed by ELISA. Compound 3a effectively prevented cognitive impairment induced by the AD model, and its effects were comparable to those of melatonin. In addition, this melatonin analogue with a donepezil fragment reduced AD-associated oxidative stress and suppressed model-associated increased Aβ1-42 levels in the hippocampus. Our findings suggest that melatonin analogs containing donepezil fragments are promising therapeutic options for targeting oxidative stress associated with AD. Full article
(This article belongs to the Special Issue Melatonin: Physiological Effects on Health and Diseases)
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Review

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15 pages, 672 KiB  
Review
Melatonin as the Missing Link Between Sleep Deprivation and Immune Dysregulation: A Narrative Review
by Ida Szataniak and Kacper Packi
Int. J. Mol. Sci. 2025, 26(14), 6731; https://doi.org/10.3390/ijms26146731 - 14 Jul 2025
Viewed by 73
Abstract
Sleep deprivation impairs immune function, and melatonin has emerged as a key mediator in this process. This narrative review analyzes 50 studies published between 2000 and 2025 to determine the extent to which reduced melatonin synthesis contributes to immune dysregulation. Consistent sleep loss [...] Read more.
Sleep deprivation impairs immune function, and melatonin has emerged as a key mediator in this process. This narrative review analyzes 50 studies published between 2000 and 2025 to determine the extent to which reduced melatonin synthesis contributes to immune dysregulation. Consistent sleep loss lowers melatonin levels, which correlates with elevated proinflammatory cytokines (e.g., IL-6 and TNF-α), increased oxidative stress, and reduced immune cell activity, including that of natural killer (NK) cells and CD4+ lymphocytes. Melatonin regulates immune pathways, including NF-κB signaling. It also supports mitochondrial health and helps maintain gut barrier integrity. These effects are particularly relevant in vulnerable populations, including older adults and shift workers. Experimental findings also highlight melatonin’s therapeutic potential in infections like SARS-CoV-2, where it modulates inflammatory responses and viral entry mechanisms. Despite the heterogeneity of study methodologies, a consistent correlation emerges between circadian disruption, melatonin suppression, and immune imbalance. These findings underscore melatonin’s dual role as a chronobiotic and immunomodulator. Addressing sleep loss and considering melatonin-based interventions may help restore immune homeostasis. More clinical trials are needed to determine the best dosing, long-term efficacy, and population-specific strategies for supplementation. Promoting healthy sleep is crucial for preventing chronic inflammation and diseases associated with immune dysfunction. Full article
(This article belongs to the Special Issue Melatonin: Physiological Effects on Health and Diseases)
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