THE NEUROPROTECTIVE EFFECT OF NON-CODING RNAS IN ISCHEMIA AND REPERFUSION OF THE BRAIN MAY BE MEDIATED BY A DECREASE IN THE LEVEL OF ATG PROTEINS

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Аннотация

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.

Авторлар туралы

I. Zakharova

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

St. Petersburg, Russia

L. Bayunova

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

St. Petersburg, Russia

N. Avrova

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: avrova@iephb.ru
St. Petersburg, Russia

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