Роль нейротрофического фактора мозга в патогенезе бронхиальной астмы у пожилых

Нейротрофический фактор мозга (brain­derived neurotrophic factor, BDNF) широко экспрессируется в нервной, иммунной, бронхолегочной системах и вовлечен в процессы клеточного старения, что обусловливает интерес к изучению его роли в патогенезе развития бронхиальной астмы (БА) у пожилых (поздняя БА). Активация BDNF может происходить не только посредством его связи с клеточными рецепторами (высокоаффинный протеин­тирозинкиназный рецептор TrkB и нетирозинкиназный низкоаффинный рецептор p75NTR), но и рецептор­независимым путем, через систему Keap1/Nrf2. Оба сигнальных пути нарушаются при БА и старении. Кроме того, описаны Keap1­независимые пути активации Nrf2, которые также связаны с активностью BDNF и участвуют в процессах старения и патогенезе БА. Стареющие клетки приобретают SASP­фенотип, который участвует в прогрессировании иммуностарения, иммуновоспаления, старения легких и способен опосредовать развитие БА у пожилых людей. С другой стороны, стареющие клетки способны экспрессировать BDNF и TrkB, которые поддерживают их жизнеспособность через SASP. Тот факт, что ингибиторы Trk способны снижать жизнеспособность стареющих клеток в эксперименте, позволяет взглянуть по­новому на роль TrkB/BDNF в качестве мишени при лечении БА у пожилых. Описана роль Nrf2 в нивелировании клеточного старения и связанного с ним SASP, что может также представлять интерес с позиций изучения его роли в патогенезе БА. В настоящем обзоре обобщена современная информация относительно BDNF, его рецепторного и рецептор­независимого действия, а также роли в иммуновоспалительных процессах, старении и патогенезе развития БА у пожилых.

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