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Targeting Epilepsy: Molecular Mechanisms, Neuroinflammation and Emerging Therapies
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Targeting Epilepsy: Molecular Mechanisms, Neuroinflammation and Emerging Therapies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 August 2026 | Viewed by 2234

Editor

Dr. Karoly Orban-Kis

E-Mail Website
Guest Editor
Department of Physiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Târgu Mureș, Romania
Interests: epilepsy; neurology; epileptogenesis; animal model of disease

Special Issue Information

Dear Colleagues,

This Special Issue presents cutting-edge advancements in the understanding and treatment of epilepsy, a complex neurological disorder characterized by recurrent, unprovoked seizures. Emphasis is placed on the identification and characterization of novel molecular targets involved in epileptogenesis, including ion channels, neurotransmitter systems, and intracellular signaling pathways. The role of neuroinflammation and immune-mediated mechanisms in seizure initiation and progression is critically examined, highlighting emerging opportunities for targeted intervention. Contributions also address advances in rational drug design, high-throughput screening, and translational models that bridge preclinical models and clinical applications and accelerate antiseizure medication discovery. By integrating insights from molecular neuroscience, pharmacology, and systems biology, this collection aims to foster interdisciplinary dialog and inform future directions in epilepsy research and therapeutic innovation.

Dr. Karoly Orban-Kis
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • epilepsy
  • molecular targets
  • antiepileptic drug discovery
  • neuroinflammation
  • epileptogenesis
  • ion channels
  • pharmacoresistance
  • translational neuroscience

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Published Papers (2 papers)

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Review

107 pages, 3117 KB  
Review
Anti-Inflammatory and Antioxidant Strategies in Epilepsy: From Molecular Mechanisms to Threshold Management
by Alexander Trofimov, Ksenia Shcherbakova, Alexander Schwarz, Burkitkan Akbay, Orynbassar Karapina, Zhuldyz Myrkhiyeva, Egor Shirokov, Bauyrzhan Kizatov, Kudiyar Zhukanov, Ayaulym Baktursyn, Madina Isseyeva, Aliya Namiyaliyeva, Alexey Sarapultsev, Maria Komelkova, Oleg Lookin and Tursonjan Tokay
Int. J. Mol. Sci. 2026, 27(15), 6606; https://doi.org/10.3390/ijms27156606 (registering DOI) - 24 Jul 2026
Abstract
Epilepsy is a multifactorial disorder, yet routine management still focuses on neuronal excitation and insufficient inhibition, with antiseizure medications (ASMs) as the primary therapeutic strategy. This approach fails in roughly one-third of patients who develop drug-resistant epilepsy (DRE). Converging evidence links DRE with [...] Read more.
Epilepsy is a multifactorial disorder, yet routine management still focuses on neuronal excitation and insufficient inhibition, with antiseizure medications (ASMs) as the primary therapeutic strategy. This approach fails in roughly one-third of patients who develop drug-resistant epilepsy (DRE). Converging evidence links DRE with neuroinflammation, oxidative stress (OS), and mitochondrial dysfunction—an interconnected distal pathophysiological triad that progressively lowers seizure thresholds yet remains peripheral to clinical epilepsy management. We map this triad mechanistically and show that ASMs modulate it beyond their anticonvulsant activity, while triad-targeting pharmacological, dietary, and botanical interventions independently reduce seizure susceptibility. Common precipitants are reinterpreted as acute activators of the distal triad, linking precipitant identification and patient agency to threshold elevation. Integrating these elements, we propose a threshold management framework for DRE, built on a revised reservoir model, and translate it into three structural priorities: mechanistic phenotyping to stratify patients by pathophysiological domain, dual-mechanism drug development, and trial designs suited to multicomponent, context-dependent interventions. Together, these proposals reframe epilepsy management from sequential pharmacological trials toward coordinated optimization of the full seizure threshold landscape. Full article
(This article belongs to the Special Issue Targeting Epilepsy: Molecular Mechanisms, Neuroinflammation and Emerging Therapies)
18 pages, 1463 KB  
Review
Neurologist’s Black Swan: Molecular Basis of Prenatal Seizures
by Angelina O. Kustova, Alexandra D. Medyanik, Polina E. Anisimova, Victor S. Tarabykin and Elena V. Kondakova
Int. J. Mol. Sci. 2026, 27(1), 283; https://doi.org/10.3390/ijms27010283 - 26 Dec 2025
Cited by 1 | Viewed by 1424
Abstract
One of the least studied but clinically severe forms of epilepsy is seizures with prenatal manifestations. Our understanding of epilepsy disorders has advanced substantially; numerous disease-associated genes have been identified, classifications have been refined, and underlying mechanisms and diagnostic approaches have been elucidated. [...] Read more.
One of the least studied but clinically severe forms of epilepsy is seizures with prenatal manifestations. Our understanding of epilepsy disorders has advanced substantially; numerous disease-associated genes have been identified, classifications have been refined, and underlying mechanisms and diagnostic approaches have been elucidated. However, one group of patients—those with seizures before the birth—has remained largely overlooked by researchers, despite numerous similar clinical cases reported over the past two decades. To date, only two genes, SCN2A and SCN8A, have been shown to have pathogenic variants that are reliably related to fetal epilepsy. Yet, how many genes are truly involved? This review will examine the known molecular foundations of epilepsy with prenatal onset. The prevalence of fetal seizures in patients with epilepsy is likely underestimated, although timely diagnosis of the disease is crucial for patient outcomes. Full article
(This article belongs to the Special Issue Targeting Epilepsy: Molecular Mechanisms, Neuroinflammation and Emerging Therapies)
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