БИОХИМИЯ, 2021, том 86, вып. 6, с. 771–786

УДК 543.51

Белок DJ-1 и его роль в развитии болезни Паркинсона: исследования на экспериментальных моделях

Обзор

© 2021 О.А. Бунеева, А.Е. Медведев *professor57@yandex.ru

НИИ биомедицинской химии имени В.Н. Ореховича, 119121 Москва, Россия

Поступила в редакцию 25.12.2020
После доработки 25.02.2021
Принята к публикации 12.03.2021

DOI: 10.31857/S0320972521060026

КЛЮЧЕВЫЕ СЛОВА: белок DJ-1, структура и функции, каталитическая активность, патогенные мутации, болезнь Паркинсона, экспериментальные модели, лиганды DJ-1.

Аннотация

DJ-1, известный также как белок 7 болезни Паркинсона (БП) (Parkinson disease protein 7), – многофункциональный белок, который экспрессируется практически во всех клетках и тканях. Взаимодействуя с белками различных внутриклеточных компартментов, DJ-1 играет важную роль в поддержании ряда клеточных функций. У мутантных форм DJ-1, содержащих аминокислотные замены (особенно L166P, характерные для БП), нарушены способность этого белка к димеризации, стабильность и фолдинг. DJ-1 проявляет несколько видов каталитической активности, однако в классификации ферментов он фигурирует как протеиндегликаза (КФ 3.5.1.124). По-видимому, в разных компартментах клетки DJ-1-белку свойственны каталитические и некаталитические функции, соотношение которых пока неизвестно. Оксидативный стресс способствует диссоциации цитоплазматических димеров DJ-1 и увеличенному поступлению образовавшихся мономеров в ядро, где этот белок действует как коактиватор различных сигнальных путей, предотвращая гибель клеток. В митохондриях DJ-1 обнаружен в составе синтасом, где он взаимодействует с β-субъединицей АТР-синтазы. При моделировании экспериментального паркинсонизма подавление экспрессии гена DJ-1 повышает чувствительность клеток к нейротоксинам, а введение рекомбинантного белка DJ-1 ослабляет проявление этой патологии. Тринадцатичленный фрагмент аминокислотной последовательности DJ-1, присоединённый к проникающему в клетки гептапептиду ТАТ-белка, проявлял нейропротекторные свойства в различных вариантах моделирования паркинсонизма как на культурах клеток, так и при введении животным. Низкомолекулярные лиганды DJ-1 также обладают терапевтическим потенциалом, оказывая нейропротекторный эффект как при инкубации с клетками, так и при введении животным.

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Финансирование

Работа выполнена в рамках Программы фундаментальных научных исследований в Российской Федерации на долгосрочный период (2021–2030 годы).

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Данная работа не предполагала использования людей и животных в качестве объектов исследования. Обобщённые в обзоре результаты исследований авторов оригинальных работ были выполнены с одобрения соответствующих комитетов по этике, указанные в каждой процитированной статье.

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