Journal of Evolutionary Biochemistry and PhysiologyJournal of Evolutionary Biochemistry and PhysiologyЖурнал эволюционной биохимии и физиологии0044-45293034-5529The Russian Academy of Sciences69705410.7868/S3034552925040023REVIEWSОБЗОРНЫЕ СТАТЬИResearch ArticleTHE NEUROPROTECTIVE EFFECT OF NON-CODING RNAS IN ISCHEMIA AND REPERFUSION OF THE BRAIN MAY BE MEDIATED BY A DECREASE IN THE LEVEL OF ATG PROTEINSНейропротекторное действие некодирующих РНК при ишемии реперфузии головного мозга может быть опосредовано снижением уровня белков ATGZakharovaI. O.ЗахароваИ. О.BayunovaL. V.БаюноваЛ. В.AvrovaN. F.АвроваН. Ф.avrova@iephb.ruSechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of SciencesИнститут эволюционной физиологии и биохимии им. И.М. Сеченова РАН15082025614VOL 61, NO4 (2025)ТОМ 61, №4 (2025)22624026112025Copyright ©; 2025, Russian Academy of SciencesCopyright ©; 2025, Российская академия наук2025Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0044-4529/article/view/697054

In recent years, it has become clear that non-coding RNAs play an important role in regulating the development, metabolism and function of various organs. They play a pronounced regulatory role in various diseases and pathological conditions, including cerebral ischemia and reperfusion. Regulatory non-coding RNAs are mainly represented by long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs). Excessive activation of autophagy during severe cerebral ischemia and subsequent reperfusion leads to autophagic neuronal death, which, with apoptotic neuronal death, is known to be one of the main causes of brain injury in this disease. This review shows that regulatory noncoding RNAs can exert a neuroprotective effect by reducing the level of autophagy-related proteins (ATG proteins), which leads to inhibition and normalization of autophagy during brain ischemia and reperfusion. Thus, knockdown of one of the lncRNAs can lead to a significant increase in the level of microRNAs, which causes a subsequent decrease in the levels of messenger RNA (mRNA) of one of the ATG proteins and, as a consequence, a decrease in the level of the ATG protein itself. This results in inhibition of autophagy and reduction in brain damage from ischemia and reperfusion injury. Changes in miRNA and target protein mRNA levels occur due to the existence of complementary nucleotide sequences in lncRNA and miRNA, as well as in miRNA and mRNA of different ATG proteins, respectively. Thus, the final decrease in the level of ATG protein and inhibition of autophagy determine the protective effect of knockout of a number of lncRNAs (or circRNAs) during brain ischemia and reperfusion. Further study of the regulatory role of noncoding RNAs may help identify ways to counteract the brain-damaging effects of overactivation of autophagy and other abnormalities during brain ischemia and reperfusion.

Многочисленные исследования показали ключевую роль некодирующих РНК в фундаментальных биологических процессах, таких как эмбриональное развитие, метаболизм и функционирование органов и тканей. К этому классу молекул относятся в основном длинные некодирующие РНК (lncRNA), микро- РНК (miRNA) и кольцевые РНК (circRNA). Велика их модулирующая роль при болезнях и патологических состояниях, в том числе при ишемии и реперфузии мозга. Одним из ключевых механизмов повреждения головного мозга при тяжелой церебральной ишемии-реперфузии является гибель нейронов, вызванная чрезмерной активацией аутофагии. Данная форма клеточной смерти вносит существенный вклад в патогенез наравне с апоптозом. В настоящем обзоре показано, что регуляторные некодирующие РНК могут оказывать нейропротекторное действие путем снижения уровня белков, связанных с аутофагией (ATG белков), которое приводит к ингибированию и нормализации аутофагии при ишемии и реперфузии мозга. Так, нокдаун одной из lncRNA может привести к значительному повышению уровня микроРНК с последующим снижением уровней информационной РНК (мРНК) одного из ATG белков и, как следствие, к снижению уровня самого белка ATG. Это вызывает ингибирование аутофагии и уменьшение повреждений головного мозга от воздействия ишемии и реперфузии. Изменения уровней микроРНК и мРНК белка-мишени в оси lncRNA (или circRNA)/miRNA/ATG белок происходят за счет наличия комплементарных нуклеотидных последовательностей у lncRNA и микроРНК, а также у микроРНК и мРНК различных ATG белков соответственно. Таким образом, конечное снижение уровняATGбелка и ингибирование аутофагии определяют защитный эффект нокаута ряда lncRNA (или circRNA) при ишемии и реперфузии мозга. Дальнейшее исследование регуляторных функций некодирующих РНК открывает перспективы для разработки стратегий, направленных на коррекцию нарушений, вызванных гиперактивацией аутофагии и иными патологическими процессами при церебральной ишемии и реперфузии.

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