Circular RNA and Alzheimer's Disease

Abstract

Circular RNAs (circRNAs) represent a special group of noncoding single-stranded highly stable ribonucleic acid entities abundant in the eukaryotic transcriptome. These circular forms of RNAs are significantly enriched in human brain and retinal tissues. However, the biological evolution and function of these circRNAs are poorly understood. Recent reports showed circRNA to be an important player in the development of neurodegenerative diseases like Alzheimer's disease. With the progression of age, circRNA level increases in the brain and also in age-associated neurological disorder like Alzheimer's disease (AD), Parkinson's disease, inflammatory neuropathy, nervous system neoplasms, and prion diseases. One highly represented circRNA in the human brain and retina is a ciRS-7 (CDR1as) which acts as an endogenous, anticomplementary miRNA inhibitor or "sponge" to quench the normal functioning of miRNA-7. Low CDR1as level can lead to increase in miR-7 expression which downregulates the activity of ubiquitin protein ligase A (UBE2A), an important AD target, functionally involved in clearing toxic amyloid peptides from AD brain. This chapter focuses on the functional relationship of circRNA with AD and interplay of miRNA-mRNA-mediated genetic regulatory networks. Our conceptual understanding also suggests that circRNA can be considered as a potential biomarker and therapeutic target in AD diagnosis and treatment.

Keywords: Alzheimer’s disease; Amyloid; CDR1as miR-7; UBE2A; circRNA.