Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment

Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102480 - 102480

Опубликована: Сен. 3, 2024

Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen nitrogen species (ROS RNS). The associated progressive accumulation molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger indirect antioxidant, is synthesized matrix neurons. Melatonin reduces ETC elevates ATP production; it also detoxifies ROS/RNS via SIRT3/FOXO pathway upregulates activities superoxide dismutase 2 glutathione peroxidase. influences glucose processing by In neurogenerative diseases, often adopt Warburg-type metabolism which excludes pyruvate mitochondria causing reduced acetyl coenzyme A production. Acetyl supports citric acid cycle OXPHOS. Additionally, required co-substrate for arylalkylamine-N-acetyl transferase, rate limits melatonin synthesis; therefore, production diminished cells that experience making more vulnerable stress. Moreover, endogenously produced diminishes during aging, further increasing components. More normal preserved aging with supplementation.

Язык: Английский

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Tryptophan metabolism-related gene CYP1B1 serves as a shared biomarker for both Parkinson’s disease and insomnia

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 8, 2025

Parkinson's disease (PD) and insomnia are prevalent neurological disorders, with emerging evidence implicating tryptophan (TRP) metabolism in their pathogenesis. However, the precise mechanisms by which TRP contributes to these conditions remain insufficiently elucidated. This study explores shared metabolism-related genes (TMRGs) molecular underlying PD insomnia, aiming provide insights into We analyzed datasets for (GSE100054) (GSE208668) obtained from Gene Expression Omnibus (GEO) database. TMRGs were Molecular Signatures Database (MSigDB) Genecards Tryptophan differentially expressed (TM-DEGs) identified intersecting (DEGs) datasets. Through Protein–Protein Interaction (PPI) network analysis, Support Vector Machine-Recursive Feature Elimination (SVM-RFE) , Extreme Gradient Boosting (XGBoost) machine learning, we Cytochrome P4501B1 (CYP1B1) Electron Transfer Flavoprotein Alpha (ETFA) as key hub genes. Subsequently, employed CIBERSORT single-sample gene set enrichment analysis (ssGSEA) further investigate association between peripheral immune activation inflammatory response. Additionally, interaction, Drug-mRNA, Transcription Factor (TF)-mRNA, competing endogenous RNA (ceRNA) networks centered on constructed explore regulatory potential drug interactions. Finally, validation through bioinformatics animal experiments CYP1B1 a promising biomarker associated both insomnia.

Язык: Английский

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Research progress on anti-aging effects and mechanisms of the new ginsenoside Compound K

Deleted Journal, Год журнала: 2025, Номер 2(1), С. 100072 - 100072

Опубликована: Янв. 31, 2025

Язык: Английский

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Cognitive Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome—Aetiology and Potential Treatments

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 1896 - 1896

Опубликована: Фев. 22, 2025

Systemic infection and inflammation impair mental function through a combination of altered attention cognition. Here, we comprehensively review the relevant literature report personal clinical observations to discuss relationship between infection, peripheral inflammation, cerebral cognitive dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Cognitive ME/CFS could result from low-grade persistent associated raised pro-inflammatory cytokines. This may be caused by both infectious non-infectious stimuli lead regional blood flow accompanied disturbed neuronal function. Immune dysregulation that manifests as subtle immunodeficiency or autoimmunity targeting one more receptors also contributing factor. Efforts reduce systemic viral reactivation improve mitochondrial energy generation have potential this highly disabling condition.

Язык: Английский

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Melatonin-Mediated Protection against Sepsis-Induced Organ Dysfunction

IntechOpen eBooks, Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

Sepsis-induced organ dysfunction represents a critical challenge in intensive care medicine, characterized by complex pathophysiological mechanisms that can lead to multiple failure and death. This review examines the fundamental underlying sepsis-induced explores therapeutic potential of melatonin, multifaceted molecule with potent antioxidant anti-inflammatory properties. We analyzed pathways involved damage during sepsis, including inflammatory cascades, oxidative stress, mitochondrial dysfunction, endothelial injury. Special attention is given melatonin’s protective effects on various systems, cardiac, pulmonary, renal, hepatic, central nervous system function sepsis. Recent evidence suggests ability modulate these pathways, combined its excellent safety profile, makes it promising agent sepsis management. Understanding applications may provide new strategies for improving outcomes septic patients.

Язык: Английский

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Melatonin and the Skin: Current Progress and Perspectives for Human Health

Journal of Investigative Dermatology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Discovery of Novel 2‐Oxindoles as Compounds with Antiglaucoma Activity

ChemMedChem, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

We have synthesized new melatonin analogs 4,6,11,12 based on 3-hydroxy-2-oxindoles (11) and hydroxy-free 2-oxindoles (4,6,12) evaluated their neuroprotective antioxidant properties as well ability to reduce intraocular pressure. Reductive amination was used obtain 5-(benzylamino)-substituted (indolin-3-yl)acetonitriles 11 (indolin-3-yl)acetic acids 12 with high yields. Compounds 4a,c, 6a 11a,d,h,j-l demonstrated IOP reduction effect in range 15-27% similar the of reference compounds timolol (12% 18%, respectively). 5-(Benzylamino)-substituted 11, unlike 4,6, inhibited lipid peroxidation 2.075-13.012 µM. Inhibition NQO2 associated also for it found that compound 11h showed best inhibitory activity an IC50 = 39 μM (vs. 64 μM). All at a concentration 30 µM do not possess mitochondrial toxicity. Moreover, no disruption tubulin polymerization observed even presence 100 compounds. Thus, 3-hydroxy-2-oxindole derivatives can be drug design first-in-class antiglaucoma drugs properties.

Язык: Английский

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Molecules in the Serotonin-Melatonin Synthesis Pathway Have Distinct Interactions with Lipid Membranes

The Journal of Physical Chemistry B, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

The neurotransmitter serotonin is involved in physiological processes such as appetite, sleep, and mood diseases anxiety depression. Traditionally, the effects of were thought to be initiated by binding its target transmembrane receptors. It also known that can bind directly membrane with high affinity modulate lipid dynamics, lateral segregation lipids, vesicular association, protein activity. We investigated if other small molecules metabolic pathway, some which are signaling while others not, have similar modulating effects. Therefore, we examined several metabolites: 5-hydroxytryptophan (5-HTP), serotonin, N-acetylserotonin (NAS), melatonin model membranes mimicking synaptic membranes. Using 2H NMR spectroscopy deuterated 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC), observed all metabolites disorder membrane-mimicking largest disordering effect was for NAS smallest tryptophan. fluorescence correlation spectroscopy, it found only promotes association did not. Furthermore, differed their distribution employing solid state 1H magic angle spinning nuclear Overhauser enhancement (NOESY) experiments simple POPC Similar results obtained mimics using molecular dynamics simulations. In conclusion, causal between modulation remains elusive, this study suggests small-molecule drugs drastic biological mediated through membrane. finding changes structure lead very different distributions possibility developing future.

Язык: Английский

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Melatonin alleviates ferroptosis triggered by cadmium via regulating ferritinophagy and iron metabolism in spermatogonia

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 14, 2025

Язык: Английский

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Melatonin Interventions in Autism Spectrum Disorder: Sleep Regulation, Behavioral Outcomes, and Challenges Across the Lifespan

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Язык: Английский

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