Tunneling nanotubes and mesenchymal stem cells: New insights into the role of melatonin in neuronal recovery

Journal of Pineal Research, Journal Year: 2022, Volume and Issue: 73(1)

Published: April 14, 2022

Efficient cell-to-cell communication is essential for tissue development, homeostasis, and the maintenance of cellular functions after injury. Tunneling nanotubes (TNTs) have emerged as a new important method communication. TNTs are primarily established between stressed unstressed cells can transport variety components. Mitochondria trafficked entities through TNTs. Transcellular mitochondria transfer permits incorporation healthy into endogenous network recipient cells, changing bioenergetic profile other functional properties may allow to recuperate from apoptotic processes return normal operating state. Mesenchymal (MSCs) form constituents target cells. This occurs under both physiological pathological conditions, leading changes in energy metabolism functions. review summarizes newly described capacity melatonin improve mitochondrial fusion/fission dynamics promote TNT formation. evidence suggests that melatonin's protective effects could be attributed its ability prevent damage injured reduce senescence, anastasis, natural cell recovery phenomenon rescues brink death. The modulation these routes intercellular by play key role increasing therapeutic potential MSCs.

Language: Английский

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The role of melatonin in amyloid beta-induced inflammation mediated by inflammasome signaling in neuronal cell lines

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Oct. 19, 2023

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. In addition to amyloid beta (Aβ) and tau, neuroinflammation a crucial element in etiology of this disease. However, relevance inflammasome-induced pyroptosis AD unknown. We aimed clarify whether anti-inflammatory effects melatonin could prevent Aβ-mediated activation inflammasome. demonstrated that Aβ upregulated NOD-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD, cysteinyl aspartate-specific proteinase caspase (caspase 1) expression SH-SY5Y neuroblastoma cells, resulting release proinflammatory cytokines, including interleukin-1β (IL-1β), interleukin-18 (IL-18) tumor necrosis factor (TNF-α). Melatonin prevented inflammasome signaling excessive cytokine caused by Aβ. found ethyl 2[(2-chlorophenyl)(hydroxy) methyl]acrylate (INF-4E, NLRP3 1 inhibitor) significantly abolished Aβ-induced expression. The increase cleaved-caspase 1, pro-IL18, cleaved-IL18 suggested occurrence pyroptosis, which was further confirmed increased N-terminal gasdermin D (N-GSDMD). plays protective role against inflammation via an inflammasome-associated mechanism essential inducing active forms cytokines pyroptosis. ability inhibit may represent turning point treatment progression.

Language: Английский

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Melatonin as a multifunctional modulator: emerging insights into its role in health, reproductive efficiency, and productive performance in livestock

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 5, 2024

Melatonin, a pleiotropic hormone plays vital role in enhancing livestock performance not only by regulating circadian rhythms but also exhibiting antioxidant, immunomodulatory, and metabolic regulatory effects that collectively improve resilience, fertility, productivity. Melatonin's synthesis is predominantly influenced light exposure, with increased production darkness; however, factors such as diet health status further modulate its levels. By helping animals adapt to environmental stressors, melatonin boosts immune responses, mitigates chronic illnesses, optimizes efficiency. Its influence extends the hypothalamic-pituitary-gonadal (HPG) axis, secretion, synchronizing estrous cycles, improving embryo viability. This results improved reproductive outcomes through protection of gametes, sperm motility, enhanced oocyte quality, all which benefit fertilization process. Additionally, positively impacts productive performance, promoting muscle growth, development, optimizing milk yield composition interaction endocrine systems. As ongoing research continues uncover broader physiological effects, supplementation emerges promising approach welfare, productivity, sustainability modern animal husbandry.

Language: Английский

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Melatonin's paradox: From therapeutic benefits to toxicity warnings

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: unknown, P. 111556 - 111556

Published: May 1, 2025

Language: Английский

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Rational Computational Design of Bergaptol Derivatives: Antioxidant Potential and CYP3A4 Inhibitory Activity

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(18)

Published: May 1, 2025

Abstract This study explores the pharmacological and antioxidant potential of functionalized bergaptol ( BER ) derivatives through computational analysis, focusing on their inhibitory activity against CYP3A4 enzyme. Using computer‐assisted design multifunctional antioxidants based chemical properties protocol, 135 were designed with mono‐, di‐, tri‐substituted modifications to optimize pharmacokinetic profiles while maintaining favorable ADMET properties. Derivatives demonstrating an improved profile–including characteristics, toxicological safety, synthetic accessibility–relative parent molecule reference set prioritized for comprehensive research. Density functional theory (DFT) calculations employed determine key reactivity parameters, including Ionization energy (IE) bond dissociation enthalpy (BDE), identifying significantly enhanced relative compound. Molecular docking studies identified promising exhibiting electrostatic hydrophobic interactions amino acid residues A:HEM 601 cofactor. These enhance compounds' binding affinity potential, underscoring therapeutic promise. analysis highlights dual role as potent selective inhibitors. The results offer significant insights into systematic agents mitigate oxidative stress profile, paving way developing novel drug candidates.

Language: Английский

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CADMA-Chem: A Computational Protocol Based on Chemical Properties Aimed to Design Multifunctional Antioxidants

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 13246 - 13246

Published: Oct. 31, 2022

A computational protocol aimed to design new antioxidants with versatile behavior is presented. It called Computer-Assisted Design of Multifunctional Antioxidants and based on chemical properties (CADMA-Chem). The desired multi-functionality consists in different methods antioxidant protection combined neuroprotection, although the can also be used pursue other health benefits. dM38 melatonin derivative as a study case illustrate detail. This was found highly promising candidate for treatment neurodegeneration, particular Parkinson’s Alzheimer’s diseases. has an oral-drug, which significantly better than Trolox scavenging free radicals, chelates redox metals, prevents ●OH production, via Fenton-like reactions, repairs oxidative damage biomolecules (lipids, proteins, DNA), acts polygenic neuroprotector by inhibiting catechol-O-methyl transferase (COMT), acetylcholinesterase (AChE) monoamine oxidase B (MAOB). To best our knowledge, CADMA-Chem currently only that simultaneously involves analyses drug-like behavior, toxicity, manufacturability, protection, receptor–ligand binding affinities. expected provide starting point helps accelerate discovery oral drugs potential prevent, or slow down, multifactorial human disorders.

Language: Английский

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The role of mitochondrial transfer via tunneling nanotubes in the central nervous system: A review

Medicine, Journal Year: 2024, Volume and Issue: 103(9), P. e37352 - e37352

Published: March 1, 2024

Tumour necrosis factor alpha-induced protein 2 (TNFAIP2) is a gene induced by tumor in endothelial cells. TNFAIP2 has important functions physiological and pathological processes, including cell proliferation, adhesion, migration, angiogenesis, inflammation, tunneling nanotube (TNT) formation tumorigenesis. Moreover, the key of TNTs. TNTs are related to signal transduction between different types considered novel means cell-to-cell communication. Mesenchymal stem cells (MSCs) pluripotent that exhibit self-renewal, multidirectional differentiation, paracrine function immune-regulating ability. MSCs can transfer mitochondria through improve target This review revealed promotes rely on for mitochondrial ameliorate dysfunction.

Language: Английский

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Melatonin as mitochondria-targeted drug

Advances in protein chemistry and structural biology, Journal Year: 2023, Volume and Issue: unknown, P. 249 - 276

Published: Jan. 1, 2023

Language: Английский

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Melatonin and its derivatives

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 197 - 238

Published: Jan. 1, 2024

Language: Английский

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Use of Cyrene™, as an alternative to dimethyl sulfoxide, as a diluent for Melatonin to determine its in vitro antimicrobial capacity

Archives of Microbiology, Journal Year: 2024, Volume and Issue: 206(11)

Published: Oct. 9, 2024

Abstract Melatonin (MLT) is a methoxyindole that has potent antioxidant actions, anti-inflammatory, and antiapoptotic capacity. However, its in vitro antibacterial capacity been the least studied of properties. Dimethylsulfoxide (DMSO) most used solvent for these tests, but it shows an antimicrobial effect if not dissolved. Cyrene™ new emerged as alternative to DMSO. Therefore, this study aimed determine MLT by MIC assays, using solvent. Likewise, solubility whether exerted any on bacterial growth at different percentages was also determined. Different dilutions with concentrations, were prepared. No inhibition caused observed. The observed because Cyrene™. maximum amount can be diluted 100% Cyrene 10 mg/mL, percentage bactericidal effect. must dissolved 5% avoid effect, so only 4 mg/mL it. no other solvents are available, role cannot adequately assessed.

Language: Английский

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