6 курс / Медицинская реабилитация, ЛФК, Спортивная медицина / МЕХАНИЗМЫ_ВЛИЯНИЯ_ИНДУЦИРУЕМОЙ_АЦЕТИЛХОЛИНЭСТЕРАЗОЙ_ОЛИГОМЕРИЗАЦИИ

91

ВЫВОДЫ

1.Изменение уровня иммуноэкспрессии синаптофизина в энторинальной коре головного мозга трансгенных APP/PS1 (Tg+) мышей, которое напрямую коррелирует с количеством амилоидных бляшек, может использоваться как инструмент для анализа влияния АХЭ-индуцированной агрегации β-

амилоидного пептида на пространственную память;

2.При анализе ингибиторной активности и токсичности ряда производных урацила выявлено соединение 35, которое способно эффективно ингибировать АХЭ головного мозга in vivo и обладает при этом достаточно низкой токсичностью, чтобы применяться на модели БА;

3.Для соединения 35 в условиях in vitro показана способность снижать АХЭ-

индуцированную агрегацию β-амилоидного пептида;

4.Соединение 35 в дозе 5 мг/кг при внутрибрющинном введении способно как купировать симптомы нарушений памяти, так и снижать количество β-

амилоидных бляшек в энторинальной коре головного мозга мышей с моделируемой БА;

5.Терапия соединением 35 приводит к увеличению в энтоинальной коре головного мозга мышей с моделью БА количества растворимого фрагмента β-

амилоидного пептида 1-40, в то время как уровень более токсичного фрагмента

1-42 остается без изменений;

6.Применение соединения 35 предотвращает снижение иммуноэкспрессии синаптофизина в энторинальной коре головного мозга мышей с моделью БА;

7.Индуцируемая АХЭ олигомеризация β-амилоида (частично устраняемая соединением 35), вносит вклад в формирование нарушений памяти в условиях генетической модели БА на мышах.

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