Метаболическое репрограммирование астроцитов и микроглии как драйвер эпилептогенеза и мишень для терапии

Аннотация

Метаболическое репрограммирование астроцитов и микроглии рассматривается как значимый компонент эпилептогенеза, ассоциированный с развитием гипервозбудимости нейронных сетей, нейровоспалением и окислительным стрессом. В обзоре проанализированы ключевые механизмы глиальной дисфункции: сдвиг к аэробному гликолизу (эффект Варбурга), митохондриальные нарушения и генерация активных форм кислорода. Эти процессы регулируются сигнальными каскадами Wnt/GSK3β и mTOR, формируя порочный круг энергетического дефицита, активации NLRP3-инфламмасомы и эксайтотоксичности. Особое внимание уделено стратегиям коррекции глиального метаболизма. Наибольший терапевтический интерес представляют системные подходы, корректирующие метаболизм (кетогенная диета, агонисты рецепторов GLP‑1 и PPAR), и высокоточные технологии селективной модуляции глиальных функций (РНК‑терапия, нанодоставка). Таргетное вмешательство в метаболизм глии открывает путь к созданию антиэпилептогенных препаратов, способных модифицировать течение болезни, а не только купировать симптомы. Однако внедрение подходов в клиническую практику требует уточнения терапевтических окон вмешательства и разработки биомаркеров глиального статуса.

Сноски

* Адресат для корреспонденции.

Вклад авторов

М.В. Захарова, А.А. Коваленко, Ю.А. Горгуль, А.П. Шварц, О.Е. Зубарева, А.Р. Харисова – написание текста статьи; Г.П. Диеспиров – подготовка иллюстраций; М.В. Захарова, А.А. Коваленко, Г.П. Диеспиров, А.В. Зайцев – редактирование текста статьи.

Финансирование

Работа выполнена при поддержке гранта РНФ 25-75-10123.

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит описания проведённых авторами исследований с использованием людей и животных в качестве объектов.

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