БИОХИМИЯ, 2021, том 86, вып. 3, с. 324–340

УДК 577.24:577.3:612.67

Роль естественных процессов старения в возникновении и патогенезе болезней, связанных с аномальным накоплением белковых агрегатов

Обзор

© 2021 Н.С. Ильинский 1*, С.В. Нестеров 1,2, Е.И. Шестопёрова 1, А.В. Фонин 1,3, В.Н. Уверский 1,4, В.И. Горделий 1,5,6

Центр исследований молекулярных механизмов старения и возрастных заболеваний, Московский физико-технический институт, 141701 Долгопрудный, Московская обл., Россия; электронная почта: ilinsky_nick@mail.ru

Институт цитохимии и молекулярной фармакологии, 115404 Москва, Россия

Институт цитологии Российской академии наук, 194064 Санкт-Петербург, Россия

Отдел молекулярной медицины, Медицинский колледж им. Морсани, Университет Южной Флориды, 33612 Тампа, США

Юлихский исследовательский центр, 52428 Юлих, Германия

Институт структурной биологии, 38000 Гренобль, Франция

Поступила в редакцию 08.08.2020
После доработки 21.08.2020
Принята к публикации 24.08.2020

DOI: 10.31857/S0320972521030040

КЛЮЧЕВЫЕ СЛОВА: протеостаз, агрегация белков, протеинопатия, старение, дисфункция митохондрий, мутации, эпигенетические изменения.

Аннотация

Старение является системной первопричиной возрастных заболеваний, в частности протеинопатий. Действительно, большинство болезней, связанных с неправильным сворачиванием белка, являются спорадическими, а вероятность их возникновения растёт по мере старения организма. В данном обзоре рассмотрен процесс образования агрегатов белков и их патогенность, устройство клеточной системы поддержания протеостаза. Показано, как токсичность агрегатов нарушает важные клеточные процессы и приводит к протеинопатиям. Проанализировано, как проявления старения (дисфункция митохондрий, дисбаланс сигнальной системы, изменения генома и эпигенома) делают возможным патогенез протеинопатий – усиливают агрегацию напрямую и через дискоординацию стресс-ответов. Проведённый анализ позволяет наметить перспективы поиска воздействий для лечения протеинопатий и достижения здорового долголетия.

Сноски

* Адресат для корреспонденции.

Финансирование

Работа выполнена при финансовой поддержке Российского фонда фундаментальных исследований в рамках научного проекта № 19-14-50506.

Благодарности

Ильинский Н.С. выражает благодарность Министерству науки и высшего образования Российской Федерации за поддержку (соглашение № 075-00337-20-03, проект FSMG-2020-0003).

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит описания каких-либо исследований с участием людей или животных в качестве объектов.

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