ABSTRACT Circular RNAs (circRNAs) comprise a new class of circular RNA species produced from precursor-mRNA by the canonical spliceosome machinery, which are now emerging as important components of the gene regulatory milieu. Circular RNAs exist in most tissues and exhibit spatial and temporal patterns of expression, which are often distinct from that of their linear isoform counterpart. Circular RNAs are particularly enriched in the tissues of the brain, where they exhibit highly dynamic patterns of expression during key stages of early brain development and have been reported to accumulate with age. The precise mechanisms by which they regulate their targets are still opaque, but in line with an important role in normal physiology, aberrant circRNA expression is associated with many common, chronic diseases. The closed circular nature of circRNAs renders them insensitive to cellular exonucleases, and accordingly, they display long half-lives. CircRNA are also present in circulating exosome and microsome compartments. This together, with their enhanced stability, renders them eminently suitable as potential biomarkers for disease incidence or progression. This review explores the role of circRNAs in brain development and neurodegenerative disease and suggests potential implications of this for diagnostics and future therapeutics.
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