Title:Circular RNAs in Alzheimer’s Disease: A New Perspective of Diagnostic
and Therapeutic Targets
Volume: 22
Issue: 9
Author(s): Omid Vakili, Pooria Asili, Zeinab Babaei, Maryam Mirahmad, Atoosa Keshavarzmotamed, Zatollah Asemi*Alireza Mafi*
Affiliation:
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for
Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical
Sciences, Isfahan, Iran
Keywords:
Circular RNAs, Alzheimer's disease, MicroRNAs, nerve degeneration, aging, targeted therapy.
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 the 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 the AD progression.
Objective: The 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 briefly
highlighted.
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 in 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.