N-Acetylcysteine (NAC): Impacts on Human Health

Antioxidants, Journal Year: 2021, Volume and Issue: 10(6), P. 967 - 967

Published: June 16, 2021

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as mucolytic compound. It has well-established safety profile, its toxicity uncommon dependent on the route of administration high dosages. Its remarkable antioxidant anti-inflammatory capacity biochemical basis several diseases related oxidative stress inflammation. The primary role NAC an stems from ability increase intracellular concentration glutathione (GSH), which most crucial biothiol responsible for cellular redox imbalance. As compound, can reduce levels tumor necrosis factor-alpha (TNF-α) interleukins (IL-6 IL-1β) by suppressing activity nuclear factor kappa B (NF-κB). Despite NAC’s relevant therapeutic potential, in experimental studies, effectiveness clinical trials, addressing different pathological conditions, still limited. Thus, purpose this chapter provide overview medicinal effects applications human health based current evidence.

Language: Английский

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Mitochondrial dysfunction: mechanisms and advances in therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 15, 2024

Abstract Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation disease progression. Particularly, mitochondrial dysfunctions identified many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, cancer. However, the multifaceted nature elusive phenotypic threshold dysfunction complicate our understanding contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among most important therapeutic targets. In recent years, strategies targeting have continuously emerged transitioned clinical trials. Advanced intervention such as using healthy replenish or replace damaged mitochondria, has shown promise preclinical trials various Mitochondrial components, mtDNA, mitochondria-located microRNA, associated proteins can be potential agents augment function immunometabolic diseases tissue injuries. Here, we review current knowledge pathophysiology concrete examples We also summarize treat perspective dietary supplements targeted therapies, well translational situation related pharmacology agents. Finally, this discusses innovations applications transplantation an advanced promising treatment.

Language: Английский

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Mitochondria and Brain Disease: A Comprehensive Review of Pathological Mechanisms and Therapeutic Opportunities

Biomedicines, Journal Year: 2023, Volume and Issue: 11(9), P. 2488 - 2488

Published: Sept. 7, 2023

Mitochondria play a vital role in maintaining cellular energy homeostasis, regulating apoptosis, and controlling redox signaling. Dysfunction of mitochondria has been implicated the pathogenesis various brain diseases, including neurodegenerative disorders, stroke, psychiatric illnesses. This review paper provides comprehensive overview intricate relationship between disease, focusing on underlying pathological mechanisms exploring potential therapeutic opportunities. The covers key topics such as mitochondrial DNA mutations, impaired oxidative phosphorylation, dynamics, calcium dysregulation, reactive oxygen species generation context disease. Additionally, it discusses emerging strategies targeting dysfunction, protective agents, metabolic modulators, gene therapy approaches. By critically analysing existing literature recent advancements, this aims to enhance our understanding multifaceted disease shed light novel interventions.

Language: Английский

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Anxiety and Brain Mitochondria: A Bidirectional Crosstalk

Trends in Neurosciences, Journal Year: 2019, Volume and Issue: 42(9), P. 573 - 588

Published: July 29, 2019

Language: Английский

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Gut Dysbiosis Dysregulates Central and Systemic Homeostasis via Suboptimal Mitochondrial Function: Assessment, Treatment and Classification Implications

Current Topics in Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 20(7), P. 524 - 539

Published: Jan. 31, 2020

The gut and mitochondria have emerged as two important hubs at the cutting edge of research across a diverse array medical conditions, including most psychiatric conditions. This article highlights interaction over course development, with an emphasis on consequences for transdiagnostic processes psychiatry, but relevance to wider As well raised levels circulating lipopolysaccharide (LPS) arising from increased permeability, loss short-chain fatty acid, butyrate, is mediator how dysbiosis modulates mitochondrial function. Reactive cells, central glia systemic immune cells are also modulated by gut, in part via impacts function these cells. Gut-driven alterations activity reactive development proposed be determinant influence system. Stress, prenatal stress, acts gut. suppression coupled LPS, drives oxidative nitrosative stress signalling that culminates activation acidic sphingomyelinase-induced ceramide. Raised ceramide negatively regulate function, both directly its negative impact daytime, arousal-promoting orexin night-time sleep-promoting pineal gland-derived melatonin. Both melatonin positively phosphorylation. Consequently, gut-mediated increases circadian rhythm regulation Butyrate, can disinhibition pyruvate dehydrogenase complex, leading conversion acetyl- CoA. Acetyl-CoA necessary co-substrate initiation melatonergic pathway therefore beneficial effects synthesis has number treatment implications utilization sodium butyrate Overall, permeability significant homeostasis especially

Language: Английский

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Potential Roles of Redox Dysregulation in the Development of Schizophrenia

Biological Psychiatry, Journal Year: 2020, Volume and Issue: 88(4), P. 326 - 336

Published: April 2, 2020

Language: Английский

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Insights into myelin dysfunction in schizophrenia and bipolar disorder

World Journal of Psychiatry, Journal Year: 2022, Volume and Issue: 12(2), P. 264 - 285

Published: Feb. 15, 2022

Schizophrenia and bipolar disorder are disabling psychiatric disorders with a worldwide prevalence of approximately 1%. Both present chronic deteriorating prognoses that impose large burden, not only on patients but also society health systems. These mental illnesses share several clinical neurobiological traits; these traits, oligodendroglial dysfunction alterations to white matter (WM) tracts could underlie the disconnection between brain regions related their symptomatic domains. WM is mainly composed heavily myelinated axons glial cells. Myelin internodes discrete axon-wrapping membrane sheaths formed by oligodendrocyte processes. ensheathment allows fast efficient conduction nerve impulses through nodes Ranvier, improving overall function neuronal circuits. Rapid precisely synchronized impulse fibers connect distant structures crucial for higher-level functions, such as cognition, memory, mood, language. Several cellular subcellular anomalies myelin oligodendrocytes have been found in postmortem samples from schizophrenia or disorder, neuroimaging techniques revealed consistent at macroscale connectomic level both disorders. In this work, evidence regarding multilevel discussed, involvement proteins key functions lineage, oligodendrogenesis myelination, highlighted. The molecular components axo-myelin unit be important targets novel therapeutic approaches disorder.

Language: Английский

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Mitochondria in the Central Nervous System in Health and Disease: The Puzzle of the Therapeutic Potential of Mitochondrial Transplantation

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 410 - 410

Published: Feb. 27, 2024

Mitochondria, the energy suppliers of cells, play a central role in variety cellular processes essential for survival or leading to cell death. Consequently, mitochondrial dysfunction is implicated numerous general and CNS disorders. The clinical manifestations include metabolic disorders, immune system, tumorigenesis, neuronal behavioral abnormalities. In this review, we focus on CNS, which has unique characteristics therefore highly dependent mitochondria. First, review mitochondria development, synaptogenesis, plasticity, behavior as well their adaptation intricate connections between different types brain. Then, sparse knowledge mechanisms exogenous uptake describe attempts determine half-life transplantation long-term effects sprouting, proteome, behavior. We further discuss potential serve tool study causal link activity Next, transplantation’s therapeutic various Finally, basic reverse—translation challenges approach that currently hinder use transplantation.

Language: Английский

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m.3243A > G-Induced Mitochondrial Dysfunction Impairs Human Neuronal Development and Reduces Neuronal Network Activity and Synchronicity

Cell Reports, Journal Year: 2020, Volume and Issue: 31(3), P. 107538 - 107538

Published: April 1, 2020

Epilepsy, intellectual and cortical sensory deficits, psychiatric manifestations are the most frequent of mitochondrial diseases. How dysfunction affects neural structure function remains elusive, mostly because a lack proper in vitro neuronal model systems with dysfunction. Leveraging induced pluripotent stem cell technology, we differentiated excitatory neurons (iNeurons) normal (low heteroplasmy) impaired (high on an isogenic nuclear DNA background from patients common pathogenic m.3243A > G variant encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS). iNeurons high heteroplasmy exhibited dysfunction, delayed maturation, reduced dendritic complexity, fewer synapses. Micro-electrode array recordings networks displayed network activity decreased synchronous bursting. Impaired energy metabolism compromised structural functional integrity could be primary drivers increased susceptibility to neuropsychiatric disease.

Language: Английский

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Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Jan. 10, 2020

Emerging evidence suggests that hierarchical status provides vulnerability to develop stress-induced depression. Energy metabolic changes in the nucleus accumbens (NAc) were recently related and depression-like behavior. Acetyl-L-carnitine (LAC), a mitochondria-boosting supplement, has shown promising antidepressant-like effects opening therapeutic opportunities for restoring energy balance depressed patients. We investigated impact NAc of antidepressant LAC treatment chronically-stressed mice using 1H-magnetic resonance spectroscopy (1H-MRS). High rank, but not low mice, as assessed with tube test, showed behavioral stress, supporting higher susceptibility high social rank depressive-like behaviors. also reduced levels several energy-related metabolites counteracted by treatment. Therefore, we reveal signature vulnerable characterized restoration neuroenergetics alterations lipid function.

Language: Английский

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