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Metabolism, Synthesis and Function of Melatonin
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Metabolism, Synthesis and Function of Melatonin

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

Deadline for manuscript submissions: closed (20 March 2025) | Viewed by 3568

Special Issue Editor

Dr. Konrad Kleszczyński

E-Mail Website
Guest Editor
Department of Dermatology, University of Münster, 48149 Münster, Germany
Interests: skin; biology of melanoma; melanogenesis; photobiology; dermatopathology; cutaneous cells; mitochondria; oxidative stress; melatonin and its metabolites
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Melatonin (N-acetyl-5-methoxytryptamine) is an indole produced mainly by the pineal gland but in peripheral organs as well. Not only melatonin itself but also its metabolites are widely detected in almost all biological systems including animals, plants, and microbes. Thus, high concentrations of this indoleamine are found in various tissues and cells, including bone marrow, lymphocytes, retina, thymus, oocytes, follicular fluid, and skin. Although it is differentially distributed in subcellular organelles due to its amphiphilic character, its highest concentration is detected mitochondria. This highly lipophilic molecule easily penetrates cellular membranes protecting proteins, enzymes, mitochondria, lipids, and DNA against oxidative damage. Melatonin is well-described as a neuroendocrine mediator with pleiotropic bioactivities such as neurotransmitter, hormonal, immunomodulator, and biological modifier actions. In clinical studies, melatonin was also shown to suppress environmentally induced erythema of skin. Namely, it exhibits the scavenging of reactive oxygen species (ROS), especially quenching hydroxyl radicals; additionally, it influences immune functions and anti-inflammatory and anti-apoptotic activities.

This Special Issue provides insights and knowledge underlying melatonin’s synthesis and function as well as components involved in mammalian cells’ melatonin metabolism.

Dr. Konrad Kleszczyński
Guest Editor

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Keywords

  • melatonin
  • metabolites of melatonin
  • skin diseases
  • treatment
  • mitochondria
  • oxidative stress
  • cell signaling
  • photobiology

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Published Papers (4 papers)

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Research

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16 pages, 3834 KiB  
Article
Melatonin Mitigates Acidosis-Induced Neuronal Damage by Up-Regulating Autophagy via the Transcription Factor EB
by Yan Shi, Zhaoyu Mi, Wei Zhao, Yue Hu, Hui Xiang, Yaoxue Gan and Shishan Yuan
Int. J. Mol. Sci. 2025, 26(3), 1170; https://doi.org/10.3390/ijms26031170 - 29 Jan 2025
Viewed by 744
Abstract
Acidosis, a common feature of cerebral ischemia and hypoxia, results in neuronal damage and death. This study aimed to investigate the protective effects and mechanisms of action of melatonin against acidosis-induced neuronal damage. SH-SY5Y cells were exposed to an acidic environment to simulate [...] Read more.
Acidosis, a common feature of cerebral ischemia and hypoxia, results in neuronal damage and death. This study aimed to investigate the protective effects and mechanisms of action of melatonin against acidosis-induced neuronal damage. SH-SY5Y cells were exposed to an acidic environment to simulate acidosis, and a photothrombotic (PT) infarction model was used to establish an animal model of cerebral ischemia of male C57/BL6J mice. Both in vivo and in vitro studies demonstrated that acidosis increased cytoplasmic transcription factor EB (TFEB) levels, reduced nuclear TFEB levels, and suppressed autophagy, as evidenced by elevated p62 levels, a higher LC3-II/LC3-I ratio, decreased synapse-associated proteins (PSD-95 and synaptophysin), and increased neuronal apoptosis. In contrast, melatonin promoted the nuclear translocation of TFEB, enhanced autophagy, and reversed neuronal apoptosis. Moreover, the role of TFEB in melatonin’s neuroprotective effects was validated by modulating TFEB nuclear translocation. In conclusion, melatonin mitigates acidosis-induced neuronal damage by promoting the nuclear translocation of TFEB, thereby enhancing autophagy. These findings offer new insights into potential treatments for acidosis. Full article
(This article belongs to the Special Issue Metabolism, Synthesis and Function of Melatonin)
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17 pages, 7960 KiB  
Article
Localization and Molecular Cloning of the ASMT Gene for Melatonin Synthesis in Pigs
by Laiqing Yan, Guangdong Li, Shoulong Deng, Likai Wang, Yiwei Wang, Zixia Shen, Depeng Yin, Pengyun Ji, Bingyuan Wang and Guoshi Liu
Int. J. Mol. Sci. 2025, 26(2), 606; https://doi.org/10.3390/ijms26020606 - 13 Jan 2025
Viewed by 729
Abstract
Melatonin is synthesized in multiple tissues and organs of pigs, and existing studies have shown the presence of the melatonin-synthesizing enzyme ASMT protein. However, the genomic information for the ASMT gene has been lacking. The aim of this study was to locate the [...] Read more.
Melatonin is synthesized in multiple tissues and organs of pigs, and existing studies have shown the presence of the melatonin-synthesizing enzyme ASMT protein. However, the genomic information for the ASMT gene has been lacking. The aim of this study was to locate the genomic information of the ASMT gene in pigs using comparative genomics analysis and then obtain the coding region information through molecular cloning. First, using the NCBI Genome Data Viewer, we found that in most animals, the AKAP17A gene is often located next to the ASMT gene, with both genes arranged in the same direction. Similarly, the P2RY8 gene is commonly adjacent to the ASMTL gene, also in the same orientation. We also discovered that the ASMTL gene is frequently adjacent to the ASMT gene and arranged in the opposite direction. Using the “three-point localization” principle, we inferred the position of the ASMT gene based on the coordinates of AKAP17A and ASMTL in pigs. Our results revealed that on the pig X chromosome, a gene called LOC110258194 is located next to the AKAP17A and ASMTL genes, and its arrangement aligns with the ASMT gene in other species. Additionally, Ensembl contains a gene, ENSSSCG00000032659, at the same position, with completely overlapping exons, though it is not annotated as ASMT. Further analysis using the TreeFam tool from EMBL-EBI and the CDD tool from NCBI revealed that LOC110258194 and ENSSSCG00000032659 do not contain the typical Maf domain of ASMTL and, thus, should not be annotated as ASMTL, but rather as the ASMT gene. Using a slow-down PCR method for high-GC content genes, we successfully cloned the full CDS region of the pig ASMT gene and identified a new transcript missing Exon 6 and Exon 7. This transcript was submitted to NCBI and assigned the GenBank accession number MW847601. Our results represent the first successful localization of the ASMT gene in pigs, the first cloning of the ASMT gene’s coding region, and the first discovery of a new transcript of the pig ASMT gene. Full article
(This article belongs to the Special Issue Metabolism, Synthesis and Function of Melatonin)
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Review

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22 pages, 3493 KiB  
Review
Melatonin’s Role in Hair Follicle Growth and Development: A Cashmere Goat Perspective
by Zibin Zheng, Zhenyu Su and Wei Zhang
Int. J. Mol. Sci. 2025, 26(7), 2844; https://doi.org/10.3390/ijms26072844 - 21 Mar 2025
Viewed by 787
Abstract
Hair follicles, unique skin appendages, undergo cyclic phases (anagen, catagen, telogen) governed by melatonin and associated molecular pathways. Melatonin, synthesized in the pineal gland, skin, and gut, orchestrates these cycles through antioxidant activity and signaling cascades (e.g., Wnt, BMP). This review examines melatonin’s [...] Read more.
Hair follicles, unique skin appendages, undergo cyclic phases (anagen, catagen, telogen) governed by melatonin and associated molecular pathways. Melatonin, synthesized in the pineal gland, skin, and gut, orchestrates these cycles through antioxidant activity and signaling cascades (e.g., Wnt, BMP). This review examines melatonin’s biosynthesis across tissues, its regulation of cashmere growth patterns, and its interplay with non-coding RNAs and the gut–skin axis. Recent advances highlight melatonin’s dual role in enhancing antioxidant capacity (via Keap1-Nrf2) and modulating gene expression (e.g., Wnt10b, CTNNB1) to promote hair follicle proliferation. By integrating multi-omics insights, we construct a molecular network of melatonin’s regulatory mechanisms, offering strategies to improve cashmere yield and quality while advancing therapies for human alopecia. Full article
(This article belongs to the Special Issue Metabolism, Synthesis and Function of Melatonin)
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15 pages, 1649 KiB  
Review
Biopolymeric Scaffolds with Melatonin for Tissue Engineering—A Review
by Beata Kaczmarek-Szczepańska and Sylwia Grabska-Zielińska
Int. J. Mol. Sci. 2025, 26(6), 2520; https://doi.org/10.3390/ijms26062520 - 11 Mar 2025
Viewed by 543
Abstract
Melatonin, a natural hormone with antioxidant, anti-inflammatory, and regenerative properties, has gained increasing attention in tissue engineering for its ability to enhance the therapeutic potential of biopolymeric scaffolds. These scaffolds, designed to mimic the extracellular matrix, provide structural support and a bioactive environment [...] Read more.
Melatonin, a natural hormone with antioxidant, anti-inflammatory, and regenerative properties, has gained increasing attention in tissue engineering for its ability to enhance the therapeutic potential of biopolymeric scaffolds. These scaffolds, designed to mimic the extracellular matrix, provide structural support and a bioactive environment for tissue regeneration. By integrating melatonin, researchers aim to create multifunctional scaffolds that promote cell proliferation, modulate inflammatory responses, and improve wound healing outcomes. Challenges in utilizing melatonin include maintaining its stability under light, heat, and oxygen exposure, and optimizing its release profile for sustained therapeutic effects. Innovative fabrication methods, such as electrospinning, 3D printing, and lyophilization, have enabled precise control over scaffold architecture and melatonin delivery. These techniques ensure enhanced interactions with target tissues and tailored regeneration processes. Combining melatonin with growth factors, cytokines, and antimicrobial agents offers the potential for multifunctional applications, from chronic wound management to bone and nerve regeneration. Continued research in this field promises transformative solutions in regenerative medicine, expanding the clinical applicability of melatonin-enriched scaffolds. This review highlights the current progress, challenges, and opportunities associated with harnessing melatonin’s therapeutic potential within tissue engineering frameworks. Full article
(This article belongs to the Special Issue Metabolism, Synthesis and Function of Melatonin)
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