Melatonergic Receptors (Mt1/Mt2) as a Potential Additional Target of Novel Drugs for Depression

Neurochemical Research, Journal Year: 2022, Volume and Issue: 47(10), P. 2909 - 2924

Published: June 11, 2022

Language: Английский

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Neuroprotective Effect of Melatonin on Sleep Disorders Associated with Parkinson’s Disease

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 396 - 396

Published: Feb. 6, 2023

Parkinson’s disease (PD) is a complex, multisystem disorder with both neurologic and systemic manifestations, which usually associated non-motor symptoms, including sleep disorders. Such disorders are commonly observed as REM behavior disorder, insomnia, sleep-related breathing disorders, excessive daytime sleepiness, restless legs syndrome periodic limb movements. Melatonin has wide range of regulatory effects, such synchronizing circadian rhythm, expected to be potential new treatment in PD patients. In fact, ongoing clinical trials melatonin highlight melatonin’s therapeutic effects this disease. Mechanistically, plays its antioxidant, anti-inflammatory, anti-excitotoxity, anti-synaptic dysfunction anti-apoptotic activities. addition, attenuates the genetic variation clock genes Baml1 Per1 restore rhythm. Together, exerts various but their specific mechanisms require further investigations.

Language: Английский

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NADPH and Mitochondrial Quality Control as Targets for a Circadian-Based Fasting and Exercise Therapy for the Treatment of Parkinson’s Disease

Cells, Journal Year: 2022, Volume and Issue: 11(15), P. 2416 - 2416

Published: Aug. 4, 2022

Dysfunctional mitochondrial quality control (MQC) is implicated in the pathogenesis of Parkinson’s disease (PD). The improper selection mitochondria for mitophagy increases reactive oxygen species (ROS) levels and lowers ATP levels. downstream effects include oxidative damage, failure to maintain proteostasis ion gradients, decreased NAD+ NADPH levels, resulting insufficient energy metabolism neurotransmitter synthesis. A ketosis-based metabolic therapy that (R)-3-hydroxybutyrate (BHB) may reverse dysfunctional MQC by partially replacing glucose as an source, stimulating mitophagy, decreasing inflammation. Fasting can potentially raise cytoplasmic increasing export ketone body-derived citrate flux through isocitrate dehydrogenase 1 (IDH1). essential cofactor nitric oxide synthase, synthesized diffuse into matrix react with electron transport chain-synthesized superoxide form peroxynitrite. Excessive peroxynitrite production cause opening permeability transition pore (mPTP) depolarize activate PINK1-dependent mitophagy. Both fasting exercise increase ketogenesis cellular NAD+/NADH ratio, both which are beneficial neuronal metabolism. In addition, engage adaptive stress response signaling pathways protect neurons against proteotoxic PD. Here, we discuss how intermittent from evening meal next-day lunch together morning exercise, when circadian most oxidized, NADP+/NADPH reduced, gene expression high, slow progression

Language: Английский

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Immunological and inflammatory effects of infectious diseases in circadian rhythm disruption and future therapeutic directions

Molecular Biology Reports, Journal Year: 2023, Volume and Issue: 50(4), P. 3739 - 3753

Published: Jan. 19, 2023

Language: Английский

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Mental health and sleep disturbances among Ukrainian refugees in the context of Russian-Ukrainian war: A preliminary result from online-survey

Sleep Medicine, Journal Year: 2023, Volume and Issue: 113, P. 342 - 348

Published: Dec. 10, 2023

Language: Английский

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Sleep and sleep disorders in people with Parkinson's disease

The Lancet Neurology, Journal Year: 2024, Volume and Issue: 23(9), P. 925 - 937

Published: Sept. 1, 2024

Language: Английский

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Schizophrenia and disruption of circadian rhythms: An overview of genetic, metabolic and clinical signs

Schizophrenia Research, Journal Year: 2023, Volume and Issue: 264, P. 58 - 70

Published: Dec. 14, 2023

A molecular clock in the suprachiasmatic nucleus of anterior hypothalamus, which is entrained by dark-light cycle and controls sleep-wake cycle, regulates circadian rhythms. The risk developing mental disorders, such as schizophrenia, has long been linked to sleep abnormalities. Additionally, a common aspect disorders disturbance, direct impact on intensity symptoms quality life patient. This relationship can be explained gene alterations CLOCK schizophrenia are also important components physiological rhythm. function dopamine adenosine rhythm should noted, these hypotheses considered most popular theories explaining pathogenesis. Therefore, determining presence causal link between two key identifying new potential targets therapy, open avenues for clinical research well psychiatric care. We review disruption at genetic, metabolic, levels. summarize data about clock-controlled genes' alterations, neurotransmitter systems' impairments, association with chronotype patients. Our findings demonstrate that either homeostatic or processes regulation disturbed. Also, we found an insufficient number studies aimed studying known biological phenomena signs schizophrenia.

Language: Английский

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Dietary Supplementation with Resveratrol Attenuates Serum Melatonin Level, Pro-Inflammatory Response and Metabolic Disorder in Rats Fed High-Fructose High-Lipid Diet under Round-the-Clock Lighting

Pathophysiology, Journal Year: 2023, Volume and Issue: 30(1), P. 37 - 47

Published: Feb. 19, 2023

This study aims to investigate the effect of resveratrol on systemic inflammatory response and metabolic disorder in rats fed a high-fructose high-lipid diet (HFHLD) exposed round-the-clock lighting (RCL). 21 adult male Wistar were randomly divided into 3 groups: control (group 1, n = 7); HFHLD for 8 weeks + (RCL) 2, RCL Resveratrol (in daily dose 5 mg/kg intragastrically 3, 7). Results show that combined reduces serum melatonin (p < 0.001) accelerates pro-inflammatory activities, oxidative stress, disorder. There is significant increase tumour necrosis factor-alpha (TNF-α) C-reactive protein (CRP) (both p 0.001), blood malondialdehyde-thiobarbituric acid adducts (MDA-TBA2) glucose 0.01), insulin concentration, homeostatic model assessment resistance (HOMA-IR) index with very low-density lipoprotein (VLDL), triacylglycerol (TAG) 0.001). At same time, decrease high-density (HDL) level observed group compared control. In group, hypomelatonaemia actions, mitigated. can cause rise reduce TNF-α CRP levels MDA-TBA2 HOMA-IR VLDL TAG while HDL increases 0.01). attenuates responses prevents considerable under RCL.

Language: Английский

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Is obstructive sleep apnea a circadian rhythm disorder?

Journal of Sleep Research, Journal Year: 2023, Volume and Issue: 32(4)

Published: March 15, 2023

Summary Obstructive sleep apnea is the most common sleep‐related breathing disorder worldwide and remains underdiagnosed. Its multiple associated comorbidities contribute to a decreased quality of life work performance as well an increased risk death. Standard treatment seems have limited effects on cardiovascular metabolic aspects disease, emphasising need for early diagnosis additional therapeutic approaches. Recent evidence suggests that dysregulation circadian rhythms, processes with endogenous rhythmicity are adjusted environment through various cues, involved in pathogenesis comorbidities. In patients obstructive apnea, altered gene expression patterns been demonstrated. respiratory events may promote disturbance intermittent hypoxia, subsequent inflammation disruption neural hormonal homeostasis. this review, current knowledge rhythm regulation, disorders summarised. Studies connect abnormalities critically evaluated. Furthermore, pathogenetic mechanisms underlie association, notably hypoxia signalling, presented. A bidirectional relationship between proposed. Approaching prove beneficial development new, personalised diagnostic, prognostic tools. However, further studies needed before clinical approach includes targeting system.

Language: Английский

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Cognitive Impairment in Multiple Sclerosis

Bioengineering, Journal Year: 2023, Volume and Issue: 10(7), P. 871 - 871

Published: July 23, 2023

Almost three million individuals suffer from multiple sclerosis (MS) throughout the world, a demyelinating disease in nervous system with increased prevalence over last five decades, and is now being recognized as one significant etiology of cognitive loss dementia. Presently, modifying therapies can limit rate relapse potentially reduce brain volume patients MS, but unfortunately cannot prevent progression or onset disability. Innovative strategies are therefore required to address areas inflammation, immune cell activation, survival that involve novel pathways programmed death, mammalian forkhead transcription factors (FoxOs), mechanistic target rapamycin (mTOR), AMP activated protein kinase (AMPK), silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), associated apolipoprotein E (APOE-ε4) gene severe acute respiratory syndrome coronavirus (SARS-CoV-2). These intertwined at levels metabolic oversight cellular metabolism dependent upon nicotinamide adenine dinucleotide (NAD+). Insight into mechanisms these provide new avenues discovery for therapeutic treatment dementia cognition occurs during MS.

Language: Английский

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