The Role of microRNAs in Epigenetic Regulation of Signaling Pathways in Neurological Pathologies

Abstract

In recent times, there has been a significant increase in researchers' interest in the functions of microRNAs and the role of these molecules in the pathogenesis of many multifactorial diseases. This is related to the diagnostic and prognostic potential of microRNA expression levels as well as the prospects of using it in personalized targeted therapy. This review of the literature analyzes existing scientific data on the involvement of microRNAs in the molecular and cellular mechanisms underlying the development of pathologies such as Alzheimer's disease, cerebral ischemia and reperfusion injury, and dysfunction of the blood-brain barrier.

Keywords: Alzheimer’s disease; RNA biology; blood–brain barrier; ischemia–reperfusion injury; miRNA; neuroinflammation; oxidative stress.

Figure 1

The process of RNA interference involving microRNAs in the example of miR-27a-3p. DNA—deoxyribonucleic acid; RNA Pol II/III—RNA polymerase II or III; pri-miRNA—primary miRNA; Drosha—class 2 ribonuclease III enzyme; DGCR8—DiGeorge syndrome critical region 8; pre-miRNA—precursor miRNA; RAN—RAs-related nuclear protein; GTP—guanosine triphosphate; Dicer—endoribonuclease Dicer or helicase with RNase motif; TRBP—transactivation response RNA binding protein; RISC—RNA-induced silencing complex; Ago2—Argonaute 2; mRNA—messenger RNA; RGS1—regulator of G protein signaling 1; FSTL1—follistatin-related protein 1; FOXO1—forkhead box protein O1, ↓—inhibition.

Figure 2

Examples of effects of various miRNAs on signaling pathways in the pathogenesis of ischemia–reperfusion brain injury. EPR = endoplasmic reticulum; BBB = blood–brain barrier; green arrows = positive biological effect of RNA interference; red arrows = negative biological effect of RNA interference. The dark blue color of the molecules indicates microRNA-3p (sense); the olive color indicates microRNA-5p (antisense); the aquamarine color indicates microRNAs with an unknown formation end from pre-microRNA.