Ацетипхопин фермента

В 1976 г. две группы исследователей, возглавляемые П. Дэвисом (медицинский факультет Эдинбургского университета) и Д. Боуэном (Институт неврологии в Лондоне), сообщили о первой достоверной биохимической аномалии, связанной с болезнью Альцгеймера. Они обнаружили, что в гиппокампе и в коре головного мозга уровень фермента холин-ацетил-трансферазы (ХАТ) может снижаться очень сильно — на 90%. ХАТ катализирует синтез ацетилхолина из его предшественников — холина и ацетилкофермента А; падение его активности отражает гибель холинэргических, т.е. выделяющих ацетилхолин, нервных окончаний в этих двух областях мозга. М.-М. Месу лам из Медицинской школы Гарвардского университета и Дж. Койл из Медицинской школы Университета Джонса Гопкинса нашли, что дегенерируют нервные окончания, принадлежащие нейронам, тела которых находятся в базальной части переднего мозга.

Данные Дэвиса и Боуэна подтвердились в работах других исследователей, и многие теперь считают, что именно эта нить в конце концов приведет к пониманию причины болезни Альцгеймера. «Ацетилхолиновая» модель позволяет объяснить и главный симптом заболевания — утрату памяти. Поскольку в гиппокампе падает уровень ХАТ, должно, по всей вероятности, уменьшаться и содержание ацетилхолина (измерить его при аутопсии нельзя). То, что холинэргические окончания в гиппокампе совершенно необходимы для функционирования механизма памяти, многократно доказано. В связи с этим вполне допустимым кажется предположение, что потеря способности к обучению при болезни Альцгеймера — прямой результат нарушения передачи ацетилхолинзависимых нервных импульсов.

Холинэргическая гипотеза предлагает и реальный путь лечения: препараты, восстанавливающие уровень ацетилхолина, могли бы оказаться эффективными при болезни Альцгеймера подобно тому, как при болезни Паркинсона ДОФА (L-диокснфенилаланин) восстанавливает передачу нервных импульсов, нарушенную из-за недостатка другого медиатора — дофамина.

К сожалению, не так легко найти безвредное и эффективное вещество, которое полностью восстанавливало бы уровень ацетилхолина или имитировало его активность. На эту роль мог бы претендовать предшественник ацетилхолина; беда, однако, в том, что при болезни Альцгеймера недостает как раз окончаний, содержащих ХАТ, которая осуществляет превращение хо- лина в медиатор. Уровень ацетилхолина могло бы поднять также соединение, ингибирующее его распад; но и здесь есть затруднение: такое лекарство будет, скорее всего, действовать не только на гиппокамп и кору, но и на те части мозга (да и на другие органы), в которых ингибирование недопустимо. Та же трудность возникает и в случае агента, который имитировал бы активность ацетилхолина.

 

 

 

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