Аутизм как проявление нарушения молекулярных механизмов регуляции развития и функций синапсов

Расстройства аутистического спектра – отдельная группа дефектов развития с очень высокой генетической компонентой. Генетический скрининг выявил множество различных генетических вариаций, связанных с аутизмом, а биоинформатический анализ сигнальных путей и генных сетей привел к пониманию, что многие из этих мутационных изменений вовлечены в функционирование синапсов. Синапс является местом электрохимической коммуникации между нейронами и необходимой субъединицей для обучения и формирования памяти. Межнейронная коммуникативная связь пластична, и наиболее стойкие формы синаптической пластичности сопровождаются изменениями в биосинтезе белка как в теле нейронов, так и локально в дендритах. Локальная трансляция – это тонко регулируемый процесс, центральную роль в регуляции инициации которого играет сигнальный путь mTOR (mammalian or mechanistic target of rapamycin). Мутационное повреждение хотя бы одного из звеньев этого сигнального пути приводит к нарушениям синаптической пластичности и поведения. С нарушениями регуляции локальной трансляции в дендритах связаны моногенные синдромы Нунана, Костелло, Каудена, Ретта, туберозный склероз, нейрофиброматоз I типа и синдром ломкой Х-хромосомы, у части носителей которых также диагностируются расстройства аутистического спектра. Данный обзор посвящен молекулярным механизмам синдромного аутизма, обусловленного моногенными мутациями, а также механизм обоснованной терапии некоторых расстройств аутистического спектра.

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