Circular RNAs in Alzheimer's Disease: A New Perspective of Diagnostic and Therapeutic Targets

Omid Vakili; Pooria Asili; Zeinab Babaei; Maryam Mirahmad; Atoosa Keshavarzmotamed; Zatollah Asemi; Alireza Mafi

doi:10.2174/1871527321666220829164211

Circular RNAs in Alzheimer's Disease: A New Perspective of Diagnostic and Therapeutic Targets

CNS Neurol Disord Drug Targets. 2022 Aug 29. doi: 10.2174/1871527321666220829164211. Online ahead of print.

Authors

Omid Vakili¹, Pooria Asili², Zeinab Babaei¹, Maryam Mirahmad², Atoosa Keshavarzmotamed³, Zatollah Asemi⁴, Alireza Mafi¹

Affiliations

¹ Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
² Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
³ Student Research Committee, Guilan University of Medical Sciences, Rasht, Iran.
⁴ Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

PMID: 36043720
DOI: 10.2174/1871527321666220829164211

Abstract

Background: Circular RNAs (circRNAs), as covalently closed single-stranded noncoding RNA molecules, have been recently identified to involve in several biological processes, principally through targeting microRNAs. Among various neurodegenerative diseases (NDs), accumulating evidence has proposed key roles for circRNAs in the pathogenesis of Alzheimer's disease (AD); although the exact relationship between these RNA molecules and AD progression is not clear, they have been believed to mostly act as miRNA sponges or gene transcription modulators through correlating with multiple proteins, involved in the accumulation of Amyloid β (Aβ) peptides, as well as tau protein, as AD's pathological hallmark. More interestingly, circRNAs have also been reported to play diagnostic and therapeutic roles during AD progression.

Objective: Literature review indicated that circRNAs could essentially contribute to the onset and development of AD. Thus, in the current review, the circRNAs' biogenesis and functions are addressed at first, and then the interplay between particular circRNAs and AD is comprehensively discussed. Eventually, the diagnostic and therapeutic significance of these noncoding RNAs is highlighted in brief.

Results: A large number of circRNAs are expressed in the brain. Thereby, these RNA molecules are noticed as potential regulators of neural functions in healthy circumstances, as well as neurological disorders. Moreover, circRNAs have also been reported to have potential diagnostic and therapeutic capacities in relation to AD, the most prevalent ND.

Conclusion: CircRNAs have been shown to act as sponges for miRNAs, thereby regulating the function of related miRNAs, including oxidative stress, reduction of neuroinflammation, and the formation and metabolism of Aβ, all of which developed in AD. CircRNAs have also been proposed as biomarkers that have potential diagnostic capacities in AD. Despite these characteristics, the use of circRNAs as therapeutic targets and promising diagnostic biomarkers will require further investigation and characterization of the function of these RNA molecules in AD.

Keywords: Aging; Alzheimer disease; Circular RNAs; MicroRNAs; Nerve degeneration; Targeted therapy..