Аннотация
Интегрированный ответ на стресс (ИОС) представляет собой консервативный для всех эукариот механизм клеточного ответа на различные сильные стрессовые сигналы, включая гипоксию, нехватку аминокислот и глюкозы, воспаление, стресс эндоплазматического ретикулума и другие. Центральным элементом ИОС является фосфорилирование эукариотического фактора инициации трансляции 2 альфа (eIF2α). Этот процесс регулируется четырьмя киназами: PERK, GCN2, HRI и PKR, каждая из которых активируется различными стрессовыми условиями. Система ИОС играет критическую роль в поддержании гомеостаза клеток и их выживании в условиях стресса, однако ее хроническая активация может привести к дисфункции клеток и программируемой клеточной смерти. Недавние исследования показывают, что ИОС активно вовлечен в патогенез нейродегенеративных заболеваний, включая болезни Альцгеймера и Паркинсона, боковой амиотрофический склероз, а также активируется при травматическом повреждении мозга. В то же время вклад ИОС в развитие психических расстройств, таких как депрессия, тревожные расстройства, шизофрения, биполярное расстройство, посттравматическое стрессовое расстройство и аддикции, остается недостаточно изученным. В работе рассматриваются современные данные о роли ИОС в патогенезе психических расстройств ЦНС, а также обсуждаются возможности терапевтической модуляции системы ИОС в контексте этих заболеваний.
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