Mitochondrial Permeability Transition, Cell Death and Neurodegeneration

Cells, Год журнала: 2024, Номер 13(7), С. 648 - 648

Опубликована: Апрель 8, 2024

Neurodegenerative diseases are chronic conditions occurring when neurons die in specific brain regions that lead to loss of movement or cognitive functions. Despite the progress understanding mechanisms this pathology, currently no cure exists treat these types diseases: for some them only help is alleviating associated symptoms. Mitochondrial dysfunction has been shown be involved pathogenesis most neurodegenerative disorders. The fast and transient permeability mitochondria (the mitochondrial transition, mPT) an initial step mechanism apoptotic necrotic cell death, which acts as a regulator tissue regeneration postmitotic it leads irreparable cells function. In study, we review role transition neuronal death major diseases, covering inductors mPTP opening neurons, including ones—free radicals calcium—and discuss perspectives difficulties development neuroprotective strategy based on inhibition

Язык: Английский

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Advancing neurological disorders therapies: Organic nanoparticles as a key to blood-brain barrier penetration

International Journal of Pharmaceutics, Год журнала: 2025, Номер 670, С. 125186 - 125186

Опубликована: Янв. 8, 2025

The blood-brain barrier (BBB) plays a vital role in protecting the central nervous system (CNS) by preventing entry of harmful pathogens from bloodstream. However, this also presents significant obstacle when it comes to delivering drugs for treatment neurodegenerative diseases and brain cancer. Recent breakthroughs nanotechnology have paved way creation wide range nanoparticles (NPs) that can serve as carriers diagnosis therapy. Regarding their promising properties, organic NPs potential be used effective drug delivery across BBB based on recent advancements. These remarkable ability penetrate using various mechanisms. This review offers comprehensive examination intricate structure distinct properties BBB, emphasizing its crucial function preserving balance regulating transport ions molecules. disruption conditions such stroke, Alzheimer's disease, Parkinson's disease highlights importance developing creative approaches drugs. Through encapsulation therapeutic molecules precise targeting processes vasculature, NP formulations present hopeful strategy improve BBB. We explore changes pathological investigate factors affect successful into brain. In addition, we most systems associated with shown positive results treating ischemic disorders. opens up new possibilities nanotechnology-based therapies cerebral diseases.

Язык: Английский

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Pirfenidone regulates seizures through the HMGB1/TLR4 axis to improve cognitive functions and modulate oxidative stress and neurotransmitters in PTZ-induced kindling in mice

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 22, 2025

Background Epilepsy is a neurological disorder characterized by recurrent seizures due to abnormal electrical activity in the brain. Pirfenidone, an antifibrotic drug, has shown anti-inflammatory and antioxidant properties various disease models, including conditions. However, its potential anticonvulsant effects have not been thoroughly explored. This study aims evaluate of pirfenidone pentylenetetrazol-induced kindling model epilepsy, focusing on effect seizure activity, cognition, profiles, inflammatory markers, neurotransmitter balance, liver enzyme levels, histopathological changes. Methods Healthy male Swiss albino mice were subjected acute Increasing Current Electroshock test chronic pentylenetetrazol-kindling model. Pirfenidone was administered at doses 100, 200, 300 mg/kg, orally, with sodium valproate as standard drug. Seizure severity cognitive function assessed model, along biochemical assays that evaluated enzymes, levels. Histopathological changes also hippocampus cortex experimental mice. Results 200 mg/kg significantly increased Threshold test, indicating protective against seizures. In delayed onset reduced severity, dose showing strongest impact. demonstrated significant improvements function, evidenced enhanced performance passive avoidance elevated plus maze tests. Antioxidant profiles showed levels superoxide dismutase, catalase, glutathione, corresponding reduction malondialdehyde acetylcholinesterase pro-inflammatory cytokines interleukin-6, interleukin-1β, transforming growth factor-β, tumor necrosis factor- α, high-mobility group box-1, toll-like receptor-4, gamma-aminobutyric acid, decreased glutamate modulated aspartate aminotransferase alanine analysis revealed ameliorated cellular disintegration neuronal damage cortex. Conclusion shows anticonvulsant, anti-inflammatory, hepatoprotective, neuroprotective agent, additional benefits improving cognition oxidative stress epilepsy treatment. Further studies are required explore long-term safety efficacy.

Язык: Английский

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A Comprehensive Review of Emerging Trends and Innovative Therapies in Epilepsy Management

Brain Sciences, Год журнала: 2023, Номер 13(9), С. 1305 - 1305

Опубликована: Сен. 11, 2023

Epilepsy is a complex neurological disorder affecting millions worldwide, with substantial number of patients facing drug-resistant epilepsy. This comprehensive review explores innovative therapies for epilepsy management, focusing on their principles, clinical evidence, and potential applications. Traditional antiseizure medications (ASMs) form the cornerstone treatment, but limitations necessitate alternative approaches. The delves into cutting-edge such as responsive neurostimulation (RNS), vagus nerve stimulation (VNS), deep brain (DBS), highlighting mechanisms action promising outcomes. Additionally, gene optogenetics in research discussed, revealing groundbreaking findings that shed light seizure mechanisms. Insights cannabidiol (CBD) ketogenic diet adjunctive further broaden spectrum management. Challenges achieving control traditional therapies, including treatment resistance individual variability, are addressed. importance staying updated emerging trends management emphasized, along hope improved therapeutic options. Future directions, combining AI applications, non-invasive optogenetics, hold promise personalized effective treatment. As field advances, collaboration among researchers natural synthetic biochemistry, clinicians from different streams various forms medicine, will drive progress toward better higher quality life individuals living

Язык: Английский

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Disorders of Endogenous and Exogenous Antioxidants in Neurological Diseases

Antioxidants, Год журнала: 2023, Номер 12(10), С. 1811 - 1811

Опубликована: Сен. 29, 2023

In diseases of the central nervous system, such as Alzheimer's disease (AD), Parkinson's (PD), stroke, amyotrophic lateral sclerosis (ALS), Huntington's (HD), and even epilepsy migraine, oxidative stress load commonly surpasses endogenous antioxidative capacity. While processes have been robustly implicated in pathogenesis these diseases, significance particular antioxidants, both especially exogenous, maintaining redox homeostasis requires further research. Among enzymes catalase, superoxide dismutase, glutathione peroxidase are to disabling free radicals, thereby preventing damage cellular lipids, proteins, nucleic acids. Whether supplementation with endogenously occurring antioxidant compounds melatonin carries any benefit, however, remains equivocal. Similarly, while health benefits certain exogenous including ascorbic acid (vitamin C), carotenoids, polyphenols, sulforaphanes, anthocyanins touted, their clinical efficacy effectiveness neurological contexts need be more defined. Here, we review current literature on mechanisms mitigating comment possible benefit most common antioxidants AD, PD, ALS, HD, epilepsy, migraine. We selected a basically neurodegenerative nature.

Язык: Английский

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The Role of Neuroinflammation and Network Anomalies in Drug-Resistant Epilepsy

Neuroscience Bulletin, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

Epilepsy affects over 50 million people worldwide. Drug-resistant epilepsy (DRE) accounts for up to a third of these cases, and neuro-inflammation is thought play role in such cases. Despite being long-debated issue the field DRE, mechanisms underlying neuroinflammation have yet be fully elucidated. The pro-inflammatory microenvironment within brain tissue with DRE has been probed using single-cell multimodal transcriptomics. Evidence suggests that inflammatory cells cytokines nervous system can lead extensive biochemical changes, as connexin hemichannel excitability disruption neurotransmitter homeostasis. presence inflammation may give rise neuronal network abnormalities suppress endogenous antiepileptic systems. We focus on anomalies from multiple perspectives identify critical points clinical application. hope provide an insightful overview advance quest better treatments.

Язык: Английский

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The Gut-Brain Axis and Neuroinflammation in Traumatic Brain Injury

Molecular Neurobiology, Год журнала: 2024, Номер 62(4), С. 4576 - 4590

Опубликована: Окт. 28, 2024

Язык: Английский

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Luteolin ameliorates pentetrazole-induced seizures through the inhibition of the TLR4/NF-κB signaling pathway

Epilepsy Research, Год журнала: 2024, Номер 201, С. 107321 - 107321

Опубликована: Фев. 14, 2024

Язык: Английский

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Oxidative stress‐related cellular aging causes dysfunction of the Kv3.1/KCNC1 channel reverted by melatonin

Aging Cell, Год журнала: 2024, Номер 23(8)

Опубликована: Май 9, 2024

Abstract The voltage‐gated Kv3.1/KCNC1 channel is abundantly expressed in fast‐spiking principal neurons and GABAergic inhibitory interneurons throughout the ascending auditory pathway various brain regions. Inactivating mutations KCNC1 gene lead to forms of epilepsy a decline expression Kv3.1 involved age‐related hearing loss. As oxidative stress plays fundamental role pathogenesis loss, we hypothesized that an insult might affect function this channel. To verify hypothesis, activity endogenous ectopic were measured models stress‐related aging represented by cell lines exposed 100 mM d‐galactose. In these models, intracellular reactive oxygen species, thiobarbituric acid substances, sulfhydryl groups cellular proteins, catalase superoxide dismutase dysregulated, while current density was significantly reduced. Importantly, antioxidant melatonin reverted all effects. reduction not determined direct oxidation amino side chains protein or transcript total levels but linked reduced trafficking surface associated with Src phosphorylation as well metabolic endoplasmic reticulum stress. data presented here specify novel target suggest dysfunction contribute loss increased prevalence during aging. pharmacological use can be protective setting.

Язык: Английский

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Unraveling the nexus of age, epilepsy, and mitochondria: exploring the dynamics of cellular energy and excitability

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Сен. 5, 2024

Epilepsy, a complex neurological condition marked by recurring seizures, is increasingly recognized for its intricate relationship with mitochondria, the cellular powerhouses responsible energy production and calcium regulation. This review offers an in-depth examination of interplay between epilepsy, mitochondrial function, aging. Many factors might account correlation epilepsy Mitochondria, integral to dynamics neuronal excitability, perform critical role in pathophysiology epilepsy. The mechanisms linking mitochondria are multifaceted, involving dysfunction, reactive oxygen species (ROS), dynamics. Mitochondrial dysfunction can trigger seizures compromising ATP production, increasing glutamate release, altering ion channel function. ROS, natural byproducts respiration, contribute oxidative stress neuroinflammation, epileptogenesis. govern fusion fission processes, influence seizure threshold buffering, impact propagation. Energy demands during highlight generation maintaining membrane potential. handling dynamically modulates affecting synaptic transmission action potential generation. Dysregulated hallmark contributing excitotoxicity. Epigenetic modifications function through histone modifications, DNA methylation, non-coding RNA expression. Potential therapeutic avenues targeting include mitochondria-targeted antioxidants, ketogenic diets, metabolic therapies. concludes outlining future directions research, emphasizing integrative approaches, advancements ethical considerations. Mitochondria emerge as central players narrative offering profound insights this challenging disorder.

Язык: Английский

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