REVIEW: Neuroprotective Effects of Peptides in the Brain: Transcriptome Approach

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I. B. Filippenkov^1,a*, L. V. Dergunova¹, S. A. Limborska¹, and N. F. Myasoedov¹

¹Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia

^* To whom correspondence should be addressed.

Received December 5, 2019; Revised December 5, 2019; Accepted December 11, 2019

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The importance of studying the action mechanisms of drugs based on natural regulatory peptides is commonly recognized. Particular attention is paid to the peptide drugs that contribute to the restoration of brain functions after acute cerebrovascular accidents (stroke), which for many years continues to be one of the main problems and threats to human health. However, molecular genetic changes in the brain in response to ischemia, as well as the mechanisms of protective effects of peptides, have not been sufficiently studied. This limits the use of neuroprotective peptides and makes it difficult to develop new, more efficient drugs with targeted action on brain functions. Transcriptome analysis is a promising approach for studying the mechanisms of the damaging effects of cerebral ischemia and neuroprotective action of peptide drugs. Beside investigating the role of mRNAs in protein synthesis, the development of new neuroprotection strategies requires studying the involvement of regulatory RNAs in ischemia. Of greatest interest are microRNAs (miRNAs) and circular RNAs (circRNAs), which are expressed predominantly in the brain. CircRNAs can interact with miRNAs and diminish their activity, thereby inhibiting miRNA-mediated repression of mRNAs. It has become apparent that analysis of the circRNA/miRNA/mRNA system is essential for deciphering the mechanisms of brain damage and repair. Here, we present the results of studies on the ischemia-induced changes in the activity of genes and peptide-mediated alterations in the transcriptome profiles in experimental ischemia and formulate the basic principles of peptide regulation in the ischemia-induced damage.

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KEY WORDS: transcriptomics, regulatory peptides, brain ischemia, mRNA, non-coding RNA, microRNA, circular RNA

DOI: 10.1134/S0006297920030037

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