Melatonin: A Cutaneous Perspective on its Production, Metabolism, and Functions

Journal of Investigative Dermatology, Год журнала: 2018, Номер 138(3), С. 490 - 499

Опубликована: Фев. 7, 2018

Язык: Английский

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Melatonin receptors: molecular pharmacology and signalling in the context of system bias

British Journal of Pharmacology, Год журнала: 2017, Номер 175(16), С. 3263 - 3280

Опубликована: Июль 14, 2017

Melatonin, N ‐acetyl‐5‐methoxytryptamine, an evolutionally old molecule, is produced by the pineal gland in vertebrates, and it binds with high affinity to melatonin receptors, which are members of GPCR family. Among multiple effects attributed melatonin, we will focus here on those that dependent activation two mammalian MT 1 2 receptors. We briefly summarize latest developments synthetic receptor ligands, including multi‐target‐directed characterization signalling‐biased ligands. discuss signalling pathways activated receptors appear be highly cell‐ tissue‐dependent, emphasizing impact system bias functional outcome. Different proteins have been demonstrated interact thus, postulate part this has its molecular basis differences expression receptor‐associated heterodimerization partners. Finally, at level receptor, genetic variants, discussed show how a modified function can effect risk for common diseases like type diabetes humans. Linked Articles This article themed section Recent Developments Research Melatonin Potential Therapeutic Applications. To view other articles visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc

Язык: Английский

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Melatonin in type 2 diabetes mellitus and obesity

Nature Reviews Endocrinology, Год журнала: 2018, Номер 15(2), С. 105 - 125

Опубликована: Дек. 7, 2018

Язык: Английский

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Melatonin: Clinical Perspectives in Neurodegeneration

Frontiers in Endocrinology, Год журнала: 2019, Номер 10

Опубликована: Июль 16, 2019

Neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's (PD) are important health problems there is a growing recognition that both governmental non-governmental organizations must make efforts to prevent, in addition treat, them. In this context, the pineal product melatonin has promising significance. Melatonin, an unusual phylogenetically conserved molecule present all known aerobic organisms, effective chronobiotic cytoprotective. As chronobiotic, afternoon increase "opens doors of sleep" every night therapeutic use been demonstrated preserve slow wave sleep effectively. cytoprotective molecule, reverses low degree inflammatory damage seen neurodegenerative disorders ageing. One characteristics advancing age gradual decrease circulating levels melatonin. Both vitro vivo, prevented neurodegeneration observed experimental models AD PD. Melatonin also increased removal toxic proteins by brain glymphatic system. A limited number clinical trials have indicated potential value neuroprotective drug treatment AD, particularly at early stage cognitive impairment, From animal studies effects need high doses become apparent (i.e. 40-100 mg/day range). The off-label discussed.

Язык: Английский

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Is Melatonin the Cornucopia of the 21st Century?

Antioxidants, Год журнала: 2020, Номер 9(11), С. 1088 - 1088

Опубликована: Ноя. 5, 2020

Melatonin, an indoleamine hormone produced and secreted at night by pinealocytes extra-pineal cells, plays important role in timing circadian rhythms (24-h internal clock) regulating the sleep/wake cycle humans. However, recent years melatonin has gained much attention mainly because of its demonstrated powerful lipophilic antioxidant free radical scavenging action. Melatonin been proven to be twice as active vitamin E, believed most effective antioxidant. Melatonin-induced signal transduction through receptors promotes expression enzymes well inflammation-related genes. also exerts immunomodulatory action stimulation high-affinity expressed immunocompetent cells. Here, we reviewed efficacy, safety side effects supplementation treating oxidative stress- and/or disorders, such obesity, cardiovascular diseases, immune infectious cancer, neurodegenerative osteoporosis infertility.

Язык: Английский

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Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery

Nature Reviews Drug Discovery, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Язык: Английский

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Circadian clock communication during homeostasis and ageing

Nature Reviews Molecular Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

Язык: Английский

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Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology

Phytomedicine, Год журнала: 2018, Номер 50, С. 257 - 284

Опубликована: Сен. 20, 2018

Adaptogens are natural compounds or plant extracts that increase adaptability and survival of organisms under stress. stimulate cellular organismal defense systems by activating intracellular extracellular signaling pathways expression stress-activated proteins neuropeptides. The effects adaptogens on mediators adaptive stress response longevity have been reported, but their stress-protective mechanisms still not fully understood.The aim this study was to identify key molecular adaptogenic plants traditionally used treat aging-related disorders, i.e., Rhodiola rosea, Eleutherococcus senticosus, Withania somnifera, Rhaponticum carthamoides, Bryonia alba.To investigate the underlying adaptogens, we conducted RNA sequencing profile gene alterations in T98G neuroglia cells upon treatment analyzed relevance deregulated genes stress-response using silico pathway analysis software.At least 88 3516 regulated were closely associated with (ASRSPs), including neuronal related corticotropin-releasing hormone, cAMP-mediated, protein kinase A, CREB; involving CXCR4, melatonin, nitric oxide synthase, GP6, Gαs, MAPK, neuroinflammation, neuropathic pain, opioids, renin-angiotensin, AMPK, calcium, synapses; dendritic cell maturation G-coupled receptor-mediated nutrient sensing enteroendocrine cells. All samples tested showed significant encoding neurohormones CRH, GNRH, UCN, G-protein-coupled other transmembrane receptors TLR9, PRLR, CHRNE, GP1BA, PLXNA4, a ligand-dependent nuclear receptor RORA, channels, transcription regulators FOS, FOXO6, SCX, STAT5A, ZFPM2, ZNF396, ZNF467, kinases MAPK10, MAPK13, MERTK, FLT1, PRKCH, ROS1, TTN), phosphatases PTPRD, PTPRR, peptidases, metabolic enzymes, chaperone (HSPA6), proteins, all which modulate numerous life processes, playing roles several canonical involved regulation homeostasis organisms. It is for first time report mechanism actions melatonin alike, activated acting through two membrane MT1 MT2 upregulation ligand-specific plays role intellectual disability, neurological retinopathy, hypertension, dyslipidemia, cancer, common aging. Furthermore, upregulated GNRH1, CHRM4, GPR19, VIPR2, TTN, commonly tested. We conclude an adaptation hormone important homeostasis. presumably worked as eustressors ("stress-vaccines") activate system inducing ASRSPs, then reciprocally protected from damage caused distress. Functional investigation interactive demonstrated ASRSPs stress-induced disorders such chronic inflammation, cardiovascular health, neurodegenerative cognitive impairment, cancer.This has elucidated genome-wide herbal brain culture. These data highlight consistent activation affected many modulation homeostasis, indicating ability modify prevent disorders. Overall, provides comprehensive look at exerts effects.

Язык: Английский

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Melatonin and Female Reproduction: An Expanding Universe

Frontiers in Endocrinology, Год журнала: 2020, Номер 11

Опубликована: Март 6, 2020

For more than a half century the hormone melatonin has been associated with vertebrate reproduction, particularly in context of seasonal breeding. This association is due large measure to fact that secretion from pineal gland into peripheral circulation nocturnal event whose duration reflective night length, which course becomes progressively longer during winter months and correspondingly shorter summer months. The plasma signal conserved essentially all vertebrates accessed not just for reproductive rhythms, but cycles metabolic activities, immune functions, behavioral expression. A vast literature on biology accrued over past 60 years since melatonin's discovery, including broad topic animal far beyond scope this human-focused review. Although modern humans industrialized world appear general have little remaining seasonality, relationships between human reproduction continue attract widespread scientific attention. purpose chapter draw attention some newer developments field, especially those relevance fertility medicine. As majority studies focused female system, discussion potential impact male will be left others.

Язык: Английский

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Membrane Melatonin Receptors Activated Cell Signaling in Physiology and Disease

International Journal of Molecular Sciences, Год журнала: 2021, Номер 23(1), С. 471 - 471

Опубликована: Дек. 31, 2021

The pineal hormone melatonin has attracted great scientific interest since its discovery in 1958. Despite the enormous number of basic and clinical studies exact role respect to human physiology remains elusive. In humans, two high-affinity receptors for melatonin, MT1 MT2, belonging family G protein-coupled (GPCRs) have been cloned identified. receptor types activate Gi proteins MT2 couples additionally Gq modulate intracellular events. individual effects activation a variety cells are complemented by their ability form homo- heterodimers, functional relevance which is yet be confirmed. Recently, several genetic polymorphisms were discovered implicated pathology—for instance type 2 diabetes, autoimmune disease, cancer. circadian patterns secretion, pleiotropic depending on cell condition, already demonstrated cross-talks with other signal transduction pathways further contribute perplexity research humans. this review we try summarize current knowledge membrane activated signaling pathology certain disease conditions including

Язык: Английский

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