БИОХИМИЯ, 2019, том 84, вып. 11, с. 1564–1577

УДК 577.112.4

Малые белки теплового шока и нейродегенеративные заболевания человека

Обзор

© 2019 Л.К. Муранова *, А.С. Рыжавская *, М.В. Судницына *, В.М. Шатов *, Н.Б. Гусев *,**

Московский государственный университет им. М.В. Ломоносова, биологический факультет, 119991 Москва, Россия; электронная почта: NBGusev@mail.ru

Поступила в редакцию 30.03.2019
После доработки 04.05.2019
Принята к публикации 27.06.2019

DOI: 10.1134/S0320972519110046

КЛЮЧЕВЫЕ СЛОВА: малые белки теплового шока, шапероноподобная активность, аморфная агрегация, β-амилоиды, посттрансляционные модификации, нейродегенеративные заболевания.

Аннотация

В обзоре представлены данные литературы и собственные экспериментальные результаты, касающиеся возможного участия малых белков теплового шока в развитии таких нейродегенеративных заболеваний, как болезни Шарко–Мари–Тута, Паркинсона, Альцгеймера и таупатии. Проанализировано влияние точечных мутаций, коррелирующих с развитием болезни Шарко–Мари–Тута, на стабильность, олигомерную структуру и шапероноподобную активность двух малых белков теплового шока HspB1 и HspB8. Показано, что точечные мутации влияют на равновесие между различными олигомерными формами HspB1, вследствие чего могут меняться шапероноподобная активность и взаимодействие с белками-партнерами, что приводит к нарушению цитоскелета и гибели нейронов. Мутации HspB8 влияют на его взаимодействие с адаптерным белком Bag3 и процесс аутофагии, что также может приводить к гибели нейронов. Представлены данные литературы о влиянии малых белков теплового шока на развитие амилоидозов различной природы. Экспериментальные данные свидетельствуют о том, что малые белки теплового шока взаимодействуют с мономерами (или малыми олигомерами) амилоидогенных белков, стабилизируют их структуру, предотвращают агрегацию и/или способствуют протеолитической деградации. Такой эффект оказывается возможным в силу того, что β-складки α-кристаллинового домена малых белков теплового шока взаимодействуют с β-складками белка-мишени и затрудняют его агрегацию. Помимо этого, малые белки теплового шока совместно с другими белками теплового шока могут способствовать разборке олигомеров, образованных амилоидогенными белками. Несмотря на существенные достижения, потребуются значительные дополнительные исследования для детального понимания роли малых белков теплового шока в защите от различных нейродегенеративных заболеваний.

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Сноски

* Автор является выпускником кафедры биохимии биологического факультета МГУ им. М.В. Ломоносова.

** Адресат для корреспонденции.

Финансирование

Работа выполнена при поддержке Российского фонда фундаментальных исследований (грант № 19-04-00038).

Благодарности

Все авторы этой работы являются выпускниками кафедры биохимии биологического факультета МГУ. Наша работа была бы невозможной, если бы она не опиралась на знания и навыки, полученные во время обучения на нашей кафедре, на традиции, заложенные основателем кафедры биохимии академиком С.Е. Севериным. В год восьмидесятилетия мы хотим пожелать кафедре биохимии больших успехов и выразить надежду, что и в будущем, несмотря на возникающие проблемы и трудности, наша кафедра будет продолжать готовить заинтересованных и грамотных специалистов-биохимиков.

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит описания выполненных авторами исследований с участием людей и использованием животных в качестве объектов.

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