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Novel Melatonin Based Therapies
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Novel Melatonin Based Therapies

A special issue of Diseases (ISSN 2079-9721).

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 59117

Special Issue Editors

Prof. Dr. Alejandro Romero Martínez

E-Mail Website
Guest Editor
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, Avda. Puerta de Hierro s/n, 28040 Madrid, Spain
Interests: melatonin; oxidative stress; inflammation; neuroblastoma; chemical warfare agents; adjunctive therapy
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Russel J. Reiter

grade E-Mail Website
Guest Editor
Department of Cellular & Structural Biology, The UT Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Interests: melatonin; free radicals of disease processes and aging; oxygen derivatives
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Germaine Escames

E-Mail Website
Co-Guest Editor
Health Sciences Technology Park, Universidad de Granada, 18071 Granada, Spain
Interests: melatonin; cancer; mucositis; mitochondria; oxidative stress; clock genes

Special Issue Information

Dear Colleagues,

Melatonin has emerged in the last decade as a promising agent to counteract most of the physiopathological events that trigger several disorders. Most of the beneficial molecular functions exerted by melatonin are due to the following: Its small size and amphiphilic nature allow the molecule to easily diffuse through any membrane, reaching cytosolic, mitochondrial and nuclear compartments. It is a potent scavenger of free radicals, both directly and indirectly, inhibiting the activity of prooxidative enzymes and stimulating antioxidant enzymes through interactions with two high-affinity G protein-coupled receptors. It can activate or inhibit crucial signaling cascades involved in cell protection and survival. It plays a dominant role as a circadian neuroendocrine transducer, immune system stimulator, and effective anti-inflammatory agent. It displays multiple direct epigenetic actions. Its efficacy is strengthened by its very low toxic hazard; even at high doses, serious adverse side effects have not been reported. In this Special Issue, we will focus on the use of melatonin as an adjuvant treatment in a wide variety of diseases, which could be of critical importance for the development of novel therapeutic strategies.

This Special Issue will serve as a forum to bring together researchers of different fields to share advances in the knowledge of the therapeutic uses of melatonin.

Prof. Dr. Alejandro Romero Martínez
Prof. Dr. Russel J. Reiter
Prof. Dr. Germaine Escames
Guest Editors

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. Diseases 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 1800 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
  • adjuvant therapy
  • cancer
  • neurodegenerative diseases
  • gastrointestinal diseases
  • sleep disorders
  • cardiovascular and blood diseases
  • diabetes
  • immune system-related diseases
  • infectious diseases
  • mitochondrial diseases
  • clinical trials

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Published Papers (5 papers)

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Review

30 pages, 1297 KiB  
Review
Empowering Melatonin Therapeutics with Drosophila Models
by Cassandra Millet-Boureima, Caroline C. Ennis, Jurnee Jamison, Shana McSweeney, Anna Park and Chiara Gamberi
Diseases 2021, 9(4), 67; https://doi.org/10.3390/diseases9040067 - 26 Sep 2021
Cited by 5 | Viewed by 7423
Abstract
Melatonin functions as a central regulator of cell and organismal function as well as a neurohormone involved in several processes, e.g., the regulation of the circadian rhythm, sleep, aging, oxidative response, and more. As such, it holds immense pharmacological potential. Receptor-mediated melatonin function [...] Read more.
Melatonin functions as a central regulator of cell and organismal function as well as a neurohormone involved in several processes, e.g., the regulation of the circadian rhythm, sleep, aging, oxidative response, and more. As such, it holds immense pharmacological potential. Receptor-mediated melatonin function mainly occurs through MT1 and MT2, conserved amongst mammals. Other melatonin-binding proteins exist. Non-receptor-mediated activities involve regulating the mitochondrial function and antioxidant cascade, which are frequently affected by normal aging as well as disease. Several pathologies display diseased or dysfunctional mitochondria, suggesting melatonin may be used therapeutically. Drosophila models have extensively been employed to study disease pathogenesis and discover new drugs. Here, we review the multiple functions of melatonin through the lens of functional conservation and model organism research to empower potential melatonin therapeutics to treat neurodegenerative and renal diseases. Full article
(This article belongs to the Special Issue Novel Melatonin Based Therapies)
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21 pages, 1027 KiB  
Review
Potential Effects of Melatonin and Micronutrients on Mitochondrial Dysfunction during a Cytokine Storm Typical of Oxidative/Inflammatory Diseases
by Virna Margarita Martín Giménez, Natalia de las Heras, León Ferder, Vicente Lahera, Russel J. Reiter and Walter Manucha
Diseases 2021, 9(2), 30; https://doi.org/10.3390/diseases9020030 - 14 Apr 2021
Cited by 19 | Viewed by 6983
Abstract
Exaggerated oxidative stress and hyper-inflammation are essential features of oxidative/inflammatory diseases. Simultaneously, both processes may be the cause or consequence of mitochondrial dysfunction, thus establishing a vicious cycle among these three factors. However, several natural substances, including melatonin and micronutrients, may prevent or [...] Read more.
Exaggerated oxidative stress and hyper-inflammation are essential features of oxidative/inflammatory diseases. Simultaneously, both processes may be the cause or consequence of mitochondrial dysfunction, thus establishing a vicious cycle among these three factors. However, several natural substances, including melatonin and micronutrients, may prevent or attenuate mitochondrial damage and may preserve an optimal state of health by managing the general oxidative and inflammatory status. This review aims to describe the crucial role of mitochondria in the development and progression of multiple diseases as well as the close relationship among mitochondrial dysfunction, oxidative stress, and cytokine storm. Likewise, it attempts to summarize the main findings related to the powerful effects of melatonin and some micronutrients (vitamins and minerals), which may be useful (alone or in combination) as therapeutic agents in the treatment of several examples of oxidative/inflammatory pathologies, including sepsis, as well as cardiovascular, renal, neurodegenerative, and metabolic disorders. Full article
(This article belongs to the Special Issue Novel Melatonin Based Therapies)
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16 pages, 2450 KiB  
Review
Toxicology of Blister Agents: Is Melatonin a Potential Therapeutic Option?
by Alejandro Romero, Eva Ramos, Francisco López-Muñoz, Cristóbal De Los Ríos, Javier Egea, Emilio Gil-Martín, René Pita, Juan J. Torrado, Dolores R. Serrano and Antonio Juberias
Diseases 2021, 9(2), 27; https://doi.org/10.3390/diseases9020027 - 10 Apr 2021
Cited by 12 | Viewed by 4618
Abstract
Blister or vesicant chemical warfare agents (CWAs) have been widely used in different military conflicts, including World War I and the Iran-Iraq War. However, their mechanism of action is not fully understood. Sulfur and nitrogen mustard exert toxic effects not only through the [...] Read more.
Blister or vesicant chemical warfare agents (CWAs) have been widely used in different military conflicts, including World War I and the Iran-Iraq War. However, their mechanism of action is not fully understood. Sulfur and nitrogen mustard exert toxic effects not only through the alkylation of thiol-bearing macromolecules, such as DNA and proteins, but also produce free radicals that can develop direct toxic effects in target organs such as the eyes, skin, and respiratory system. The lack of effective treatments against vesicant CWAs-induced injury makes us consider, in this complex scenario, the use and development of melatonin-based therapeutic strategies. This multifunctional indoleamine could facilitate neutralization of the oxidative stress, modulate the inflammatory response, and prevent the DNA damage, as well as the long-term health consequences mediated by vesicant CWAs-induced epigenetic mechanisms. In this context, it would be essential to develop new galenic formulations for the use of orally and/or topically applied melatonin for the prophylaxis against vesicant CWAs, as well as the development of post-exposure treatments in the near future. Full article
(This article belongs to the Special Issue Novel Melatonin Based Therapies)
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16 pages, 797 KiB  
Review
Divergent Importance of Chronobiological Considerations in High- and Low-dose Melatonin Therapies
by Rüdiger Hardeland
Diseases 2021, 9(1), 18; https://doi.org/10.3390/diseases9010018 - 9 Mar 2021
Cited by 16 | Viewed by 3919
Abstract
Melatonin has been used preclinically and clinically for different purposes. Some applications are related to readjustment of circadian oscillators, others use doses that exceed the saturation of melatonin receptors MT1 and MT2 and are unsuitable for chronobiological purposes. Conditions are outlined [...] Read more.
Melatonin has been used preclinically and clinically for different purposes. Some applications are related to readjustment of circadian oscillators, others use doses that exceed the saturation of melatonin receptors MT1 and MT2 and are unsuitable for chronobiological purposes. Conditions are outlined for appropriately applying melatonin as a chronobiotic or for protective actions at elevated levels. Circadian readjustments require doses in the lower mg range, according to receptor affinities. However, this needs consideration of the phase response curve, which contains a silent zone, a delay part, a transition point and an advance part. Notably, the dim light melatonin onset (DLMO) is found in the silent zone. In this specific phase, melatonin can induce sleep onset, but does not shift the circadian master clock. Although sleep onset is also under circadian control, sleep and circadian susceptibility are dissociated at this point. Other limits of soporific effects concern dose, duration of action and poor individual responses. The use of high melatonin doses, up to several hundred mg, for purposes of antioxidative and anti-inflammatory protection, especially in sepsis and viral diseases, have to be seen in the context of melatonin’s tissue levels, its formation in mitochondria, and detoxification of free radicals. Full article
(This article belongs to the Special Issue Novel Melatonin Based Therapies)
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15 pages, 1236 KiB  
Review
Can Melatonin Be a Potential “Silver Bullet” in Treating COVID-19 Patients?
by Daniel P. Cardinali, Gregory M. Brown and Seithikurippu R. Pandi-Perumal
Diseases 2020, 8(4), 44; https://doi.org/10.3390/diseases8040044 - 26 Nov 2020
Cited by 55 | Viewed by 35012
Abstract
The therapeutic potential of melatonin as a chronobiotic cytoprotective agent to counteract the consequences of COVID-19 infections has been advocated. Because of its wide-ranging effects as an antioxidant, anti-inflammatory, and immunomodulatory compound, melatonin could be unique in impairing the consequences of SARS-CoV-2 infection. [...] Read more.
The therapeutic potential of melatonin as a chronobiotic cytoprotective agent to counteract the consequences of COVID-19 infections has been advocated. Because of its wide-ranging effects as an antioxidant, anti-inflammatory, and immunomodulatory compound, melatonin could be unique in impairing the consequences of SARS-CoV-2 infection. Moreover, indirect evidence points out to a possible antiviral action of melatonin by interfering with SARS-CoV-2/angiotensin-converting enzyme 2 association. Melatonin is also an effective chronobiotic agent to reverse the circadian disruption of social isolation and to control delirium in severely affected patients. As a cytoprotector, melatonin serves to combat several comorbidities such as diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases, which aggravate COVID-19 disease. In view of evidence on the occurrence of neurological sequels in COVID-19-infected patients, another putative application of melatonin emerges based on its neuroprotective properties. Since melatonin is an effective means to control cognitive decay in minimal cognitive impairment, its therapeutic significance for the neurological sequels of SARS-CoV-2 infection should be considered. Finally, yet importantly, exogenous melatonin can be an adjuvant capable of augmenting the efficacy of anti-SARS-CoV-2 vaccines. We discuss in this review the experimental evidence suggesting that melatonin is a potential “silver bullet” in the COVID 19 pandemic. Full article
(This article belongs to the Special Issue Novel Melatonin Based Therapies)
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