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Biomolecules
Special Issues
Melatonin in Health and Disease
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Melatonin in Health and Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 21071

Special Issue Editor

Dr. Christophe Ribelayga

E-Mail Website
Guest Editor
Department of Vision Sciences, College of Optometry, Graduate Program in Physiological Optics & Vision Science, University of Houston, Houston, TX, USA
Interests: circadian rhythms; retina; gap junctions; melatonin; dopamine

Special Issue Information

Dear Colleagues,

We are welcoming submissions for a Special Issue on “Melatonin in Health and Disease” is being prepared for the journal Biomolecules.

Melatonin is primarily produced by the pineal gland with a marked daily rhythm, and the night-restricted secretion of melatonin reflects the presence and duration of the sleep cycle. While the role of pineal melatonin in the organization of seasonal rhythms in mammals has been well-characterized, melatonin production outside of the pineal gland has now been firmly demonstrated, and we know much more about the local effects of melatonin on many other aspects of our physiology.

Melatonin receptors have been found in many tissues and organs. Their activation can phase-shift or entrain circadian rhythms, lower temperature, or induce sleepiness. Alterations in melatonin profiles are associated with some biological rhythm disorders, such as sleep disorders or jet lag, and melatonin or melatonin agonists have been used to successfully treat these disorders. Aside from the chronobiotic effects of melatonin, its antioxidant properties may also offer therapeutic benefits for a variety of diseases, including cancer. However, despite decades of research and the clear demonstration of melatonin’s therapeutic usage, our understanding of melatonin function in health and diseases, and its full therapeutic potential, remains limited.  

The aim of this Special Issue is to highlight progress in our understanding of melatonin’s biological functions in health and disease. We also encourage the submission of reviews on this topic.

Dr. Christophe Ribelayga
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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • melatonin
  • melatonin receptors
  • pineal gland
  • chronobiology

Published Papers (5 papers)

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Research

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15 pages, 1694 KiB  
Article
Escherichia coli RimI Encodes Serotonin N-Acetyltransferase Activity and Its Overexpression Leads to Enhanced Growth and Melatonin Biosynthesis
by Kyungjin Lee and Kyoungwhan Back
Biomolecules 2023, 13(6), 908; https://doi.org/10.3390/biom13060908 - 30 May 2023
Cited by 1 | Viewed by 1232
Abstract
Serotonin N-acetyltransferase (SNAT) functions as the penultimate or final enzyme in melatonin biosynthesis, depending on the substrate. The Escherichia coli orthologue of archaeal SNAT from Thermoplasma volcanium was identified as RimI (EcRimI), with 42% amino acid similarity to archaeal SNAT. EcRimI has [...] Read more.
Serotonin N-acetyltransferase (SNAT) functions as the penultimate or final enzyme in melatonin biosynthesis, depending on the substrate. The Escherichia coli orthologue of archaeal SNAT from Thermoplasma volcanium was identified as RimI (EcRimI), with 42% amino acid similarity to archaeal SNAT. EcRimI has been reported to be an N-acetyltransferase enzyme. Here, we investigated whether EcRimI also exhibits SNAT enzyme activity. To achieve this goal, we purified recombinant EcRimI and examined its SNAT enzyme kinetics. As expected, EcRimI showed SNAT activity toward various amine substrates including serotonin and 5-methoxytryptamine, with Km and Vmax values of 531 μM and 528 pmol/min/mg protein toward serotonin and 201 μM and 587 pmol/min/mg protein toward 5-methoxytryptamine, respectively. In contrast to the rimI mutant E. coli strain that showed no growth defect, the EcRimI overexpression strain exhibited a 2-fold higher growth rate than the control strain after 24 h incubation in nutrient-rich medium. The EcRimI overexpression strain produced more melatonin than the control strain in the presence of 5-methoxytryptamine. The enhanced growth effect of EcRimI overexpression was also observed under cadmium stress. The higher growth rate associated with EcRimI expression was attributed to increased protein N-acetyltransferase activity, increased synthesis of melatonin, or the combined effects of both. Full article
(This article belongs to the Special Issue Melatonin in Health and Disease)
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Review

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30 pages, 4943 KiB  
Review
Unveiling the Protective Role of Melatonin in Osteosarcoma: Current Knowledge and Limitations
by Nojoud Al-Ansari, Samson Mathews Samuel and Dietrich Büsselberg
Biomolecules 2024, 14(2), 145; https://doi.org/10.3390/biom14020145 - 24 Jan 2024
Viewed by 1477
Abstract
Melatonin, an endogenous neurohormone produced by the pineal gland, has received increased interest due to its potential anti-cancer properties. Apart from its well-known role in the sleep–wake cycle, extensive scientific evidence has shown its role in various physiological and pathological processes, such as [...] Read more.
Melatonin, an endogenous neurohormone produced by the pineal gland, has received increased interest due to its potential anti-cancer properties. Apart from its well-known role in the sleep–wake cycle, extensive scientific evidence has shown its role in various physiological and pathological processes, such as inflammation. Additionally, melatonin has demonstrated promising potential as an anti-cancer agent as its function includes inhibition of tumorigenesis, induction of apoptosis, and regulation of anti-tumor immune response. Although a precise pathophysiological mechanism is yet to be established, several pathways related to the regulation of cell cycle progression, DNA repair mechanisms, and antioxidant activity have been implicated in the anti-neoplastic potential of melatonin. In the current manuscript, we focus on the potential anti-cancer properties of melatonin and its use in treating and managing pediatric osteosarcoma. This aggressive bone tumor primarily affects children and adolescents and is treated mainly by surgical and radio-oncological interventions, which has improved survival rates among affected individuals. Significant disadvantages to these interventions include disease recurrence, therapy-related toxicity, and severe/debilitating side effects that the patients have to endure, significantly affecting their quality of life. Melatonin has therapeutic effects when used for treating osteosarcoma, attributed to its ability to halt cancer cell proliferation and trigger apoptotic cell death, thereby enhancing chemotherapeutic efficacy. Furthermore, the antioxidative function of melatonin alleviates harmful side effects of chemotherapy-induced oxidative damage, aiding in decreasing therapeutic toxicities. The review concisely explains the many mechanisms by which melatonin targets osteosarcoma, as evidenced by significant results from several in vitro and animal models. Nevertheless, if further explored, human trials remain a challenge that could shed light and support its utility as an adjunctive therapeutic modality for treating osteosarcoma. Full article
(This article belongs to the Special Issue Melatonin in Health and Disease)
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26 pages, 831 KiB  
Review
Melatonin: Facts, Extrapolations and Clinical Trials
by J. A. Boutin, D. J. Kennaway and R. Jockers
Biomolecules 2023, 13(6), 943; https://doi.org/10.3390/biom13060943 - 05 Jun 2023
Cited by 15 | Viewed by 3609
Abstract
Melatonin is a fascinating molecule that has captured the imagination of many scientists since its discovery in 1958. In recent times, the focus has changed from investigating its natural role as a transducer of biological time for physiological systems to hypothesized roles in [...] Read more.
Melatonin is a fascinating molecule that has captured the imagination of many scientists since its discovery in 1958. In recent times, the focus has changed from investigating its natural role as a transducer of biological time for physiological systems to hypothesized roles in virtually all clinical conditions. This goes along with the appearance of extensive literature claiming the (generally) positive benefits of high doses of melatonin in animal models and various clinical situations that would not be receptor-mediated. Based on the assumption that melatonin is safe, high doses have been administered to patients, including the elderly and children, in clinical trials. In this review, we critically review the corresponding literature, including the hypotheses that melatonin acts as a scavenger molecule, in particular in mitochondria, by trying not only to contextualize these interests but also by attempting to separate the wheat from the chaff (or the wishful thinking from the facts). We conclude that most claims remain hypotheses and that the experimental evidence used to promote them is limited and sometimes flawed. Our review will hopefully encourage clinical researchers to reflect on what melatonin can and cannot do and help move the field forward on a solid basis. Full article
(This article belongs to the Special Issue Melatonin in Health and Disease)
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14 pages, 901 KiB  
Review
Melatonin in Health and Disease: A Perspective for Livestock Production
by Zully E. Contreras-Correa, Riley D. Messman, Rebecca M. Swanson and Caleb O. Lemley
Biomolecules 2023, 13(3), 490; https://doi.org/10.3390/biom13030490 - 07 Mar 2023
Cited by 4 | Viewed by 3546
Abstract
Mounting evidence in the literature indicates an important role of endogenous and exogenous melatonin in driving physiological and molecular adaptations in livestock. Melatonin has been extensively studied in seasonally polyestrous animals whereby supplementation studies have been used to adjust circannual rhythms in herds [...] Read more.
Mounting evidence in the literature indicates an important role of endogenous and exogenous melatonin in driving physiological and molecular adaptations in livestock. Melatonin has been extensively studied in seasonally polyestrous animals whereby supplementation studies have been used to adjust circannual rhythms in herds of animals under abnormal photoperiodic conditions. Livestock undergo multiple metabolic and physiological adaptation processes throughout their production cycle which can result in decreased immune response leading to chronic illness, weight loss, or decreased production efficiency; however, melatonin’s antioxidant capacity and immunostimulatory properties could alleviate these effects. The cardiovascular system responds to melatonin and depending on receptor type and localization, melatonin can vasodilate or vasoconstrict several systemic arteries, thereby controlling whole animal nutrient partitioning via vascular resistance. Increased incidences of non-communicable diseases in populations exposed to circadian disruption have uncovered novel pathways of neurohormones, such as melatonin, influence health, and disease. Perturbations in immune function can negatively impact the growth and development of livestock which has been examined following melatonin supplementation. Specifically, melatonin can influence nutrient uptake, circulating nutrient profiles, and endocrine profiles controlling economically important livestock growth and development. This review focuses on the physiological, cellular, and molecular implications of melatonin on the health and disease of domesticated food animals. Full article
(This article belongs to the Special Issue Melatonin in Health and Disease)
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10 pages, 2731 KiB  
Review
Possible Application of Melatonin in Long COVID
by Daniel P. Cardinali, Gregory M. Brown and Seithikurippu R. Pandi-Perumal
Biomolecules 2022, 12(11), 1646; https://doi.org/10.3390/biom12111646 - 07 Nov 2022
Cited by 13 | Viewed by 10679
Abstract
Clinical sequelae and symptoms for a considerable number of COVID-19 patients can linger for months beyond the acute stage of SARS-CoV-2 infection, “long COVID”. Among the long-term consequences of SARS-CoV-2 infection, cognitive issues (especially memory loss or “brain fog”), chronic fatigue, myalgia, and [...] Read more.
Clinical sequelae and symptoms for a considerable number of COVID-19 patients can linger for months beyond the acute stage of SARS-CoV-2 infection, “long COVID”. Among the long-term consequences of SARS-CoV-2 infection, cognitive issues (especially memory loss or “brain fog”), chronic fatigue, myalgia, and muscular weakness resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are of importance. Melatonin may be particularly effective at reducing the signs and symptoms of SARS-CoV-2 infection due to its functions as an antioxidant, anti-inflammatory, and immuno-modulatory agent. Melatonin is also a chronobiotic medication effective in treating delirium and restoring the circadian imbalance seen in COVID patients in the intensive care unit. Additionally, as a cytoprotector, melatonin aids in the prevention of several COVID-19 comorbidities, including diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases. This narrative review discusses the application of melatonin as a neuroprotective agent to control cognitive deterioration (“brain fog”) and pain in the ME/CFS syndrome-like documented in long COVID. Further studies on the therapeutic use of melatonin in the neurological sequelae of SARS-CoV-2 infection are warranted. Full article
(This article belongs to the Special Issue Melatonin in Health and Disease)
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