Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of mortality among individuals with epilepsy, particularly those with drug-resistant forms. This review explores the complex multisystem mechanisms underpinning SUDEP, integrating recent findings on brain, cardiac, and pulmonary dysfunctions. Background/Objectives: The main objective of this review is to elucidate how seizures disrupt critical physiological systems, especially the brainstem, heart, and lungs, contributing to SUDEP, with emphasis on respiratory control failure and autonomic instability. Methods: The literature from experimental models, clinical observations, neuroimaging studies, and genetic analyses was systematically examined. Results: SUDEP is frequently preceded by generalized tonic–clonic seizures, which trigger central and obstructive apnea, hypoventilation, and cardiac arrhythmias. Brainstem dysfunction, particularly in areas such as the pre-Bötzinger complex and nucleus tractus solitarius, plays a central role. Genetic mutations affecting ion channels (e.g., SCN1A, KCNQ1) and neurotransmitter imbalances (notably serotonin and GABA) exacerbate autonomic dysregulation. Risk is compounded by a prone sleeping position, reduced arousal capacity, and impaired ventilatory responses. Conclusions: SUDEP arises from a cascade of interrelated failures in respiratory and cardiac regulation initiated by seizure activity. The recognition of modifiable risk factors, implementation of monitoring technologies, and targeted therapies such as serotonergic agents may reduce mortality. Multidisciplinary approaches integrating neurology, cardiology, and respiratory medicine are essential for effective prevention strategies.

Aging and aging-related neurodegenerative disorders, such as Alzheimer’s disease, are characterized by chronic inflammation that progressively damages nervous tissue within the central nervous system (CNS). In addition to cytokines, lectin-like carbohydrate recognition molecules play a critical role in modifying cellular communication during inflammation. Among these, galectins—particularly anti-inflammatory galectin-1 and pro-inflammatory galectin-3—stand out due to their immunological functions and specificity for N-acetyllactosamine structures. Almost every cell type within the CNS can express and recognize galectins, influencing various essential cellular functions. N-acetyllactosamines, the ligand structures recognized by galectins, are found beneath sialylated termini in protein-linked oligosaccharides. During aging, protein-linked oligosaccharide structures become shorter, exposing N-acetyllactosamines on protein surfaces, which enhances their availability as binding sites for galectins. Genomic studies indicate that the number of galectin-1- and galectin-3-expressing microglial cells increases with age- or age-related disease (Alzheimer’s disease), reflecting an aging-associated rise in galectin concentrations within the CNS. This increase parallels a rise in free N-acetyllactosamine-like ligands, suggesting that galectin-N-acetyllactosamine interactions gain prominence and play a more significant role in aging-related CNS disorders. Understanding these interactions and their molecular implications offers potential avenues for targeted therapeutic strategies in combating aging-related CNS inflammation and neurodegeneration.

Epilepsy affects more than 50 million individuals worldwide, and approximately one-third of patients remain refractory to existing antiseizure medications. Advances in gene therapy and genome editing have opened new possibilities for disease-modifying interventions that directly target the molecular and circuit-level mechanisms underlying epileptogenesis. Recent progress in central nervous system tropic viral vectors, non-viral delivery systems, and programmable genome-editing technologies has enabled precise manipulation of neuronal and glial function in preclinical epilepsy models. Strategies range from restoration of haploinsufficient genes implicated in monogenic epilepsies, such as SCN1A in Dravet syndrome, to modulation of neuronal excitability through engineered ion channels, neuropeptides, and astrocyte-based approaches. In parallel, CRISPR-derived platforms, including transcriptional activation and repression systems, base editing, and prime editing, offer new avenues for regulating gene expression in post-mitotic neurons without introducing double-strand DNA breaks. Despite these advances, significant translational challenges remain, including efficient and cell-type-specific delivery, long-term safety, and the risk of network-level side effects in the epileptic brain. This review critically examines recent gene therapy and genome-editing approaches for epilepsy, highlights key technological and biological barriers to clinical translation, and discusses emerging strategies that may enable durable and targeted treatments for drug-resistant epilepsies.

Aging and aging-related neurodegenerative disorders, such as Alzheimer’s disease, are characterized by chronic inflammation that progressively damages nervous tissue within the central nervous system (CNS). In addition to cytokines, lectin-like carbohydrate-recognition molecules play a critical role in modifying cellular communication during inflammation. Among these, galectins-particularly the anti-inflammatory galectin-1 and the pro-inflammatory galectin-3-stand out due to their immunological functions and specificity for N-acetyllactosamine structures. Almost every cell type within the CNS can express and recognize galectins, influencing various essential cellular functions. N-acetyllactosamines, the ligand structures recognized by galectins, are found beneath sialylated termini in protein-linked oligosaccharides. During aging, protein-linked oligosaccharide structures become shorter, exposing N-acetyllactosamines on protein surfaces, which enhances their availability as binding sites for galectins. Genomic studies indicate that the number of galectin-1- and galectin-3-expressing microglial cells increases with age or age related disease (Alzheimer’s disease), reflecting an aging-associated rise in galectin concentrations within the CNS. This increase parallels a rise in free N-acetyllactosamine-like ligands, suggesting that galectin-N-acetyllactosamine interactions gain prominence and play a more significant role in aging-related CNS disorders. Understanding these interactions and their molecular implications offers potential avenues for targeted therapeutic strategies in combating aging-related CNS inflammation and neurodegeneration

Graphical Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of mortality among individuals with epilepsy, particularly those with drug-resistant forms. This re-view explores the complex multisystem mechanisms underpinning SUDEP, integrating recent findings on brain, cardiac, and pulmonary dysfunctions. Background/Objectives: The main objective of this review is to elucidate how seizures disrupt critical physiological systems, especially the brainstem, heart, and lungs, contributing to SUDEP, with empha-sis on respiratory control failure and autonomic instability. Methods: We systematically examined literature from experimental models, clinical observations, neuroimaging stud-ies, and genetic analyses. Sources were drawn from recent peer-reviewed publications cataloged in a supplementary reference matrix. Results: SUDEP is frequently preceded by generalized tonic-clonic seizures, which trigger central and obstructive apnea, hypoventi-lation, and cardiac arrhythmias. Brainstem dysfunction, particularly in areas such as the pre-Bötzinger complex and nucleus tractus solitarius, plays a central role. Genetic muta-tions affecting ion channels (e.g., SCN1A, KCNQ1) and neurotransmitter imbalances (no-tably serotonin and GABA) exacerbate autonomic dysregulation. Risk is compounded by prone sleeping position, reduced arousal capacity, and impaired ventilatory responses. Conclusions: SUDEP arises from a cascade of interrelated failures in respiratory and car-diac regulation initiated by seizure activity. Recognition of modifiable risk factors, imple-mentation of monitoring technologies, and targeted therapies such as serotonergic agents may reduce mortality. Multidisciplinary approaches integrating neurology, cardiology, and respiratory medicine are essential for effective prevention strategies.

Physiological aging can alter the brain endothelial glycocalyx and blood–brain barrier (BBB), while experimental seizures independently engage galectin-3 (Gal-3) and inflammasome-associated inflammatory signaling. This narrative review critically examines whether these observations justify a shared mechanism in aging-associated epilepsy. Primary studies support endothelial mucin-type O-glycosylation as a determinant of BBB integrity and Gal-3 as a modulator of inflammation in selected seizure models. They do not establish that endothelial glycan remodeling changes Gal-3 binding or initiates epileptogenesis. We distinguish extracellular galectin-glycan recognition from intracellular inflammasome signaling and address the anatomical separation between parenchymal microglia and the luminal glycocalyx. Glycan elongation, ligand density, terminal modifications, and steric accessibility could alter binding in different directions; uniform exposure of galectin ligands cannot be assumed. Galectin-1 also has context-dependent protective and detrimental effects. We propose compartment-resolved experiments combining glycan measurements, cell-specific perturbations, BBB assessment, and longitudinal electroencephalography to test the convergence hypothesis.