Circular RNAs — a modern perspective on the molecular mechanisms of neurologic diseases in humans and prospects for therapeutic agents

Abstract

In mammals, many classes of noncoding RNAs (ncRNAs) are expressed at a much higher level in the brain than in other organs. Recent studies have identified a new class of ncRNAs called circular RNAs (circRNAs), which are produced by back-splicing and fusion of either exons, introns, or both exon-intron into covalently closed loops. The circRNAs are also highly enriched in the brain and increase continuously from the embryonic to the adult stage.Although the functional significance and mechanism of action of circRNAs are still being actively explored, they are thought to regulate the transcription of their host genes and sequestration of miRNAs and RNA binding proteins. Some circRNAs are also shown to have translation potential to form peptides. The expression and abundance of circRNAs seem to be spatiotemporally maintained in a normal brain.Altered expression of circRNAs is also thought to mediate several disorders, including brain-tumor growth, and acute and chronic neurodegenerative disorders by affecting mechanisms such as angiogenesis, neuronal plasticity, autophagy, apoptosis, and inflammation. These extraordinary peculiarities make circRNAs potentially suitable as promising molecular biomarkers, especially of neurodegenerative diseases. This review represents generalisation of the new data about circRNAs, underlining their role in a pathogenesis of the basic neurodegenerative disorders: emphasizing their role in pathogenesis of major neurodegenerative disorders, Alzheimers disease, frontotemporal dementia, and Parkinsons diseases, schizophrenia diseases, ALS with a look toward their potential usefulness in biomarker searching.