Аномальные белки

Каковы бы ни были ее истинные причины, при болезни Альцгеймера в мозгу всегда присутствуют аномальные белковые структуры. Их три основных типа: нейрофибриллярные клубки внутри нейронов, амилоид, который окружает и пронизывает кровеносные сосуды мозга, и богатые амилоидом тельца, которые формируются на месте дегенерировавших нервных окончаний. Все эти образования отражают накопление белков, которое в здоровом мозгу не происходит. Что собой представляют нейрофибриллярные клубки и амилоид? Скопления ли это нормальных белков или же их белки качественно аномальны, т.е. отличаются по последовательности аминокислот от нормальных белков мозга?

Если эти белки аномальные, то откуда они берутся? Быть может, за их синтез отвечают аномальные гены? Или они образуются из белков-предшественников, которые кодируются нормальными генами, но затем подвергаются неправильной модификации, возможно аномальным ферментом или ферментом, который ненормально активирован (например, токсином, попавшим в организм из внешней среды)?

Не белки ли причина наблюдаемой гибели нейронов? Если да, то потому ли, что они токсичны для нервных клеток или же нейроны выводятся из строя просто механически, когда эти белки заполняют их собой? Могут белки быть тем инфекционным агентом, который вызывает болезнь? А что если скопления белка никак не связаны с гибелью нейронов и появляются только как свидетельство того, что это уже произошло? Лишь на некоторые из этих вопросов мы начинаем получать ответы. Отчасти их может дать изучение самих белков.

Пучки белковых волокон, известные как нейрофибриллярные клубки, обнаруживаются внутри тел нейронов гиппокампа и коры головного мозга. Их также много в нервных клетках ствола головного мозга, выделяющих медиаторы (прежде всего ацетнлхолин), недостаток которых наблюдается при болезни Альцгеймера. Как заметил еще А. Альцгеймер в 1907 г., нейрофибриллярные клубки связывают красители, содержащие серебро, благодаря чему становятся видимыми в обычном световом микроскопе сначала, на ранней стадии болезни, как темные зоны в цитоплазме клетки, а позднее как большие волокнистые массы, искажающие клеточное тело. Эти образования устойчивы к химической или энзиматической обработке и нерастворимы в воде, а поэтому сохраняются в мозговой ткани еще долго после гибели и исчезновения того нейрона, в котором они возникли.

 

 

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