Сфингозин‑1‑фосфат – ключевая сигнальная молекула в норме и при рассеянном склерозе

Аннотация

Сфингозин‑1‑фосфат (S1P) представляет собой одну из наиболее изученных биоактивных сигнальных молекул сфинголипидного обмена, которая выполняет центральную роль в регуляции множества процессов в ЦНС и иммунной системе. Действуя как внеклеточный лиганд для пяти подтипов G‑белок-связанных рецепторов (S1P‑R₁–S1P‑R₅), а также как внутриклеточный медиатор метаболизма, S1P контролирует миграцию лимфоцитов, проницаемость гематоэнцефалического барьера, выживание и дифференцировку олигодендроцитов, реактивность астроцитов и микроглии, а также баланс между воспалением, нейродегенерацией и нейропротекцией. В патогенезе демиелинизирующих заболеваний, в частности рассеянного склероза, наблюдается нарушение «сфинголипидного реостата» – происходит сдвиг в сторону преобладания проапоптотических церамидов и относительного снижения уровня S1P, что способствует преобладанию процессов нейровоспаления и нейродегенерации над ремиелинизацией. В данном обзоре обобщены современные данные о структуре, метаболизме, внутри- и внеклеточных сигнальных путях S1P, о его двойственной роли в норме и при рассеянном склерозе, а также проанализированы подходы к фармакологической модуляции сигнальных путей S1P, подчёркивая перспективы селективной таргетной терапии, направленной на иммуномодуляцию, нейропротекцию и стимуляцию ремиелинизации.

Сноски

* Адресат для корреспонденции.

Вклад авторов

Д.А. Ганин – поиск и анализ литературы, написание текста статьи. М.Н. Захарова – постановка идеи и концепции обзора, редактирование текста, научное руководство.

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит описания каких-либо исследований с участием людей или животных в качестве объектов.

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