Unveiling the role of histone deacetylases in neurological diseases: focus on epilepsy

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Nov. 19, 2024

Abstract Epilepsy remains a prevalent chronic neurological disease that is featured by aberrant, recurrent and hypersynchronous discharge of neurons poses great challenge to healthcare systems. Although several therapeutic interventions are successfully utilized for treating epilepsy, they can merely provide symptom relief but cannot exert disease-modifying effect. Therefore, it urgent need explore other potential mechanism develop novel approach delay the epileptic progression. Since approximately 30 years ago, histone deacetylases (HDACs), versatile epigenetic regulators responsible gene transcription via binding histones or non-histone substrates, have grabbed considerable attention in drug discovery. There also substantial evidences supporting aberrant expressions and/activities HDAC isoforms reported epilepsy inhibitors (HDACi) been purposes this condition. However, specific mechanisms underlying role HDACs progression not fully understood. Herein, we reviewed basic information HDACs, summarized recent findings associated with roles diverse subunits discussed regulatory which affected development epilepsy. Additionally, provided brief discussion on as promising targets treatment, serving valuable reference study clinical translation field.

Language: Английский

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Glycyrrhizin as a potential disease-modifying therapy for epilepsy: insights into targeting pyroptosis to exert neuroprotective and anticonvulsant effects

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 6, 2025

For patients with epilepsy, antiseizure medication remains the primary treatment; however, it is ineffective in approximately 30% of cases. These experience progressive neuronal damage and poor outcomes. Therefore, there an urgent need for disease-modifying therapy (DMT) that targets pathogenesis epilepsy. Glycyrrhizin has shown potential as a DMT epilepsy due to its multiple diverse mechanisms. Previous studies suggest glycyrrhizin may regulate key processes involved pathogenesis, such neuroinflammation cell death, but effects on pyroptosis have not been reported. This study employed bioinformatics techniques identify molecular treatment then validated using kainic acid-induced status epilepticus mouse model. significantly prolonged seizure latency, reduced duration, alleviated Molecular experiments indicated through mediation high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway. exerts neuroprotective anticonvulsant by regulating via HMGB1/TLR4/NF-κB pathway, offering novel insights into

Language: Английский

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The Role of Glial Cells in the Pathophysiology of Epilepsy

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 94 - 94

Published: Jan. 10, 2025

Epilepsy is a chronic neurological disorder marked by recurrent seizures, significantly impacting individuals worldwide. Current treatments are often ineffective for third of patients and can cause severe side effects, necessitating new therapeutic approaches. Glial cells, particularly astrocytes, microglia, oligodendrocytes, emerging as crucial targets in epilepsy management. Astrocytes regulate neuronal homeostasis, excitability, synaptic plasticity, playing key roles maintaining the blood-brain barrier (BBB) mediating neuroinflammatory responses. Dysregulated astrocyte functions, such reactive astrogliosis, lead to abnormal activity seizure generation. They release gliotransmitters, cytokines, chemokines that may exacerbate or mitigate seizures. Microglia, innate immune cells CNS, contribute neuroinflammation, glutamate excitotoxicity, balance between excitatory inhibitory neurotransmission, underscoring their dual role promotion protection. Meanwhile, primarily involved myelination, also modulate axonal excitability neuron-glia network underlying pathogenesis. Understanding dynamic interactions glial with neurons provides promising avenues novel therapies. Targeting these improved control better clinical outcomes, offering hope refractory epilepsy.

Language: Английский

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The Relationship Between Attitudes Toward Epilepsy and Health Literacy in Turkey: The Mediating Role of Epilepsy Knowledge

Seizure, Journal Year: 2025, Volume and Issue: 125, P. 186 - 191

Published: Jan. 18, 2025

Language: Английский

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Targeting Kv7 Potassium Channels for Epilepsy

CNS Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Voltage-gated Kv7 potassium channels, particularly Kv7.2 and Kv.7.3 play a critical role in modulating susceptibility to seizures, mutations genes that encode these channels cause heterogeneous epilepsy phenotypes. On the basis of this evidence, activation has long been considered an attractive target search for novel antiseizure medications. Ezogabine (retigabine), first Kv7.2/3 activator introduced 2011 treatment focal was withdrawn from market 2017 due declining use after discovery its association with pigmentation changes retina, skin, mucosae. A formulation ezogabine pediatric (XEN496) recently investigated children KCNQ2-related developmental epileptic encephalopathy, but trial terminated prematurely reasons unrelated safety. Among openers clinical development, azetukalner shown dose-dependent efficacy against drug-resistant seizures good tolerability profile no evidence pigmentation-related adverse effects early studies, it is now under investigation phase III trials generalized tonic-clonic major depressive disorder. Another activator, BHV-7000, completed I studies healthy subjects, excellent at plasma drug concentrations exceed median effective preclinical model anticonvulsant activity, data patients are available date. other activators development as potential medications, pynegabine CB-003 have safety pharmacokinetic results not yet reported. Overall, interest targeting indications remains strong. Future breakthroughs area could come exploitation mechanistic differences action activators, molecules combine mechanisms action.

Language: Английский

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Real-world safety evaluation of brivaracetam: insights from the US FDA adverse event reporting system

Expert Opinion on Drug Safety, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Brivaracetam (BRV) is a novel drug for the treatment of epilepsy. This study aimed to detect and characterize adverse events (AEs) associated with BRV from first quarter 2016 second 2024 using U.S. Food Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. We utilized disproportionality analysis methods, including reporting odds ratio (ROR), proportional (PRR), Bayesian confidence propagation neural network (BCPNN), multi-item gamma Poisson shrinker (MGPS), assess associations between reported AEs usage in FAERS data. A total 1,781 event reports were analyzed, as primary suspected drug. identified 13 positive system organ classes (SOCs) 78 preferred term signals (PTs), particular focus on nervous disorders, psychiatric injury, poisoning, procedural complications. Exposures related complications during pregnancy lactation showed signals, exposure before pregnancy, breastfeeding, pregnancy. These exposures warrant significant attention. Based database, we conducted comprehensive BRV. aims provide guidance clinical application epilepsy treatment, thereby improving its safety.

Language: Английский

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Using Immunoliposomes as Carriers to Enhance the Therapeutic Effectiveness of Macamide N-3-Methoxybenzyl-Linoleamide

Neurology International, Journal Year: 2025, Volume and Issue: 17(3), P. 38 - 38

Published: March 3, 2025

Background/Objectives: Epilepsy is one of the most common chronic neurological disorders, characterized by alterations in neuronal electrical activity that result recurrent seizures and involuntary body movements. Anticonvulsants are primary treatment for this condition, helping patients improve their quality life. However, development new drugs with fewer side effects greater economic accessibility remains a key focus nanomedicine. Macamides, secondary metabolites derived from Maca (Lepidium meyenii), represent promising class novel diverse therapeutic applications, particularly disorders. Methods: In study, we optimized potential macamide N-3-methoxybenzyl-linoleamide (3-MBL) as an anticonvulsant agent through its encapsulation PEGylated liposomes conjugated OX26 F(ab′)2 fragments. Results: These immunoliposomes exhibited size 120.52 ± 9.46 nm zeta −8.57 0.80 mV. Furthermore, vivo tests using pilocarpine-induced status epilepticus model revealed provided efficacy against epileptic compared to free form at same dose. Notably, observed effect was comparable carbamazepine, traditional FDA-approved antiepileptic drug. Conclusions: This pioneering work employs liposomal nanocarriers deliver macamides brain, aiming set standard use modified epilepsy treatment.

Language: Английский

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A multi-stage fusion deep learning framework merging local patterns with attention-driven contextual dependencies for cancer detection

Computers in Biology and Medicine, Journal Year: 2025, Volume and Issue: 189, P. 109916 - 109916

Published: March 6, 2025

Language: Английский

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Real‐world effectiveness and tolerability of cenobamate in drug‐resistant epilepsy: A retrospective analysis of the patients included into the Early Access Programs (EAP) in Germany, France, and United Kingdom

Epilepsia Open, Journal Year: 2025, Volume and Issue: unknown

Published: March 22, 2025

Abstract Objective Investigate real‐world outcomes in drug‐resistant epilepsy (DRE) patients treated with cenobamate as adjunctive treatment to other antiseizure medications (ASMs) within the Early Access Programs (EAP) Germany, France, and United Kingdom. Methods DRE adults uncontrolled focal‐onset seizures were included from 19 hospitals participating EAP this retrospective study. Data sourced clinical records. Participants evaluated at baseline, 1 months, 3 months start, 3, 6, 12 after maintenance. The primary effectiveness endpoint was 50% responder rate, defined reduction seizure frequency ≥50%. Results collected 298 who received least one dose of cenobamate; efficacy on 216 data available. At median duration 22.2 years, 41.9% had previous surgery, including vagus nerve stimulation, a nine previously failed ASMs. number seizures/month 8.8. After maintenance, rate (primary endpoint) 49.3%; percentage baseline 49.1%. A total 100%, ≥90%, ≥75% reported 13.6%, 20.0%, 33.6% patients, respectively. Both steadily increased during observation period. 6‐month seizure‐free 24.2%. retention assessed by Kaplan–Meier decreased 96.6% 1‐month start 69.7% 12‐month Adverse Drug Reactions (ADRs) occurred 30.9% asthenia, dizziness, somnolence being most frequent; majority mild‐to‐moderate resolved period; three (1.0%) experienced seven serious ADRs, all titration. Significance In study, demonstrated be an effective option for people even multiple ASMs or failure surgery. Plain Language Summary This study involved epilepsy, continued despite using two (ASMs). Patients (Ontozry) Program An allows receive promising new drugs under supervision before they are commercially 6 49.3% their cut half more, 13.6% became seizure‐free. undesirable reaction cenobamate, mostly resolved; frequent somnolence.

Language: Английский

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Huperzine A attenuates epileptic seizures via enhancing dCA1-projecting septal cholinergic transmission

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Language: Английский

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