Кольцевые РНК — современный взгляд на молекулярный механизм неврологических заболеваний человека. Перспективы поиска новых терапевтических средств

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Аннотация

У млекопитающих отдельные виды некодирующих РНК (нкРНК) содержатся в большом количестве и сильно экспрессированы в тканях мозга, более чем в других органах. В недавних исследованиях идентифицирован новый класс нкРНК, названный кольцевыми РНК (кольцРНК), которые происходят путем слияния экзонов или интронов или обоих интронов в ковалентно-замкнутые кольца. Кольцевые РНК являются также высокоэкспрессированными в тканях мозга человека и их уровень непрерывно увеличивается от эмбрионального до взрослого состояния. Хотя функциональное значение и механизм действия кольцРНК все еще активно исследуются, они, как уже выяснено, регулируют транскрипцию своих организменных генов и секвестрацию РНК-связывающих белков и микроРНК. Отдельные кольцРНК также осуществляют трансляцию своих транскриптов при формировании пептидов. Экспрессия и распространенность кольцРНК пространственно-временным образом локализованы в тканях нормального мозга. Изменения в экспрессии кольцРНК, как полагают, вызывают ряд нарушений, включая рост опухолей головного мозга, а также острые и хронические нейродегенеративные нарушения, сопровождающиеся ключевыми механизмами, такими как ангиогенез, нейронная пластичность, аутофагия, апоптоз и воспаление. Эти необычные особенности делают кольцРНК потенциально подходящими молекулярными биомаркерами, особенно при нейродегенеративных заболеваниях. Представленный обзор обобщает новые данные о кольцРНК, подчеркивая их роль в патогенезе основных нейродегенеративных расстройств: болезни Альцгеймера, болезни Паркинсона, бокового амиотрофического склероза, эпилепсии, шизофрении, лобно-височной деменции с учетом их потенциальной полезности в качестве диагностических биомаркеров.

Об авторах

Петр Дмитриевич Шабанов

Военно-медицинская академия им. С.М. Кирова

Автор, ответственный за переписку.
Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
SPIN-код: 8974-7477

д-р мед. наук, профессор, заведующий отделом нейрофармакологии им. С.В. Аничкова

Россия, Санкт-Петербург

Владимир Иванович Ващенко

Военно-медицинская академия им. С.М. Кирова

Email: vladimir-vaschenko@yandex.ru

д-р биол. наук, ведущий научный сотрудник Центра крови и тканей

Россия, Санкт-Петербург

Лидия Павловна Савельева

Военно-медицинская академия им. С.М. Кирова

Email: lidalab@rambler.ru

заведующая клинической лабораторией Центра крови и тканей

Россия, Санкт-Петербург

Юлия Евгеньевна Ромашова

Военно-медицинская академия им. С.М. Кирова

Email: pdshabanov@mail.ru
ORCID iD: 0000-0002-5771-0789
SPIN-код: 3921-7090

заведующая отделом Центра крови и тканей

Россия, Санкт-Петербург

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© Шабанов П.Д., Ващенко В.И., Савельева Л.П., Ромашова Ю.Е., 2023

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