БЕЛКИ ТЕПЛОВОГО ШОКА ПРИ КОНФОРМАЦИОННЫХ БОЛЕЗНЯХ МОЗГА
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Ключевые слова

протеостаз
белки теплового шока
нейродегенеративные заболевания
фармакологические индукторы Hsp70
нейропротекция

Как цитировать

Белан, Д. В., & Екимова, И. В. (2019). БЕЛКИ ТЕПЛОВОГО ШОКА ПРИ КОНФОРМАЦИОННЫХ БОЛЕЗНЯХ МОЗГА. Российский физиологический журнал им. И. М. Сеченова, 105(12), 1465–1485. https://doi.org/10.1134/S0869813919120021

Аннотация

Во всем мире отмечается неуклонный рост числа фатальных хронических нейродегенеративных заболеваний, к которым относятся болезнь Паркинсона, болезнь Альцгеймера, хорея Гентингтона, амиотрофический латеральный склероз и др. Эти заболевания относят к конформационным болезням мозга, поскольку в основе патогенеза болезней этого типа лежит нарушение трехмерной пространственной укладки определенных нейрональных белковых молекул, что сопровождается изменением конформации белков, образованием в пораженных клетках токсичных олигомеров и нерастворимых белковых агрегатов. Для поддержания протеостаза и предотвращения накопления потенциально токсичных белковых агрегатов клетки используют взаимосвязанные молекулярные сети. В настоящем обзоре представлены современные данные об организации протеостазной сети, которая включает механизмы, контролирующие биогенез, фолдинг и рефолдинг, транспортировку, дезагрегацию и деградацию белков. Основное внимание уделено белкам теплового шока семейства HSP70 и малым шаперонам sHSPs, выступающим в качестве центральных координаторов протеостазной сети. Описаны клинико-морфологические проявления и патогенетические механизмы развития наиболее распространенных конформационных болезней мозга и представлены последние данные о ключевой роли шаперонов HSP70 и sHSPs в защите клеток от последствий неправильного фолдинга и агрегации белка. Рассмотрены основные достижения доклинических исследований известных на сегодняшний день фармакологических индукторов белков теплового шока в нейропротективной терапии конформационных болезней мозга.

https://doi.org/10.1134/S0869813919120021
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