CircRNAs in Alzheimer's disease: What are the prospects?

Ozal Beylerli; Aferin Beilerli; Tatiana Ilyasova; Alina Shumadalova; Huaizhang Shi; Albert Sufianov

doi:10.1016/j.ncrna.2023.11.011

CircRNAs in Alzheimer's disease: What are the prospects?

Noncoding RNA Res. 2023 Nov 26;9(1):203-210. doi: 10.1016/j.ncrna.2023.11.011. eCollection 2024 Mar.

Authors

Ozal Beylerli¹, Aferin Beilerli², Tatiana Ilyasova³, Alina Shumadalova⁴, Huaizhang Shi⁵, Albert Sufianov^{6

7}

Affiliations

¹ Central Research Laboratory, Bashkir State Medical University, Ufa, Republic of Bashkortostan, 3 Lenin Street, 450008, Russia.
² Department of Obstetrics and Gynecology, Tyumen State Medical University, 54 Odesskaya Street, 625023, Tyumen, Russia.
³ Department of Internal Diseases, Bashkir State Medical University, Ufa, Republic of Bashkortostan, 450008, Russia.
⁴ Department of General Chemistry, Bashkir State Medical University, Ufa, Republic of Bashkortostan, 3 Lenin Street, 450008, Russia.
⁵ Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
⁶ Educational and Scientific Institute of Neurosurgery, Рeoples' Friendship University of Russia (RUDN University), Moscow, Russia.
⁷ Department of Neurosurgery, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.

Abstract

Circular RNAs (circRNAs) is a fascinating covalently closed circular non-coding RNA that is abundantly present in the transcriptome of eukaryotic cells. Its versatile nature allows it to participate in a multitude of pathological and physiological processes within the organism. One of its crucial functions is acting as a microRNA sponge, modulating protein transcription levels, and forming interactions with essential RNA-binding proteins. Remarkably, circRNAs demonstrates a specific enrichment in various vital areas of the brain, including the cortex, hippocampus, white matter, and photoreceptor neurons, particularly in aging organisms. This intriguing characteristic has led scientists to explore its potential as a significant biological marker of neurodegeneration, offering promising insights into neurodegenerative diseases like Alzheimer's disease (AD). In AD, there has been an interesting observation of elevated levels of circRNAs in both peripheral blood and synaptic terminals of affected individuals. This intriguing finding raises the possibility that circRNAs may have a central role in the initiation and progression of AD. Notably, different categories of circRNAs, including HDAC9, HOMER1, Cwc27, Tulp4, and PTK2, have been implicated in driving the pathological changes associated with AD through diverse mechanisms. For instance, these circRNAs have been demonstrated to contribute to the accumulation of beta-amyloid, which is a hallmark characteristic of AD. Additionally, these circRNAs contribute to the excessive phosphorylation of tau protein, a phenomenon associated with neurofibrillary tangles, further exacerbating the disease. Moreover, they are involved in aggravating neuroinflammation, which is known to play a critical role in AD's pathogenesis. Lastly, these circRNAs can cause mitochondrial dysfunction, disrupting cellular energy production and leading to cognitive impairment. As researchers delve deeper into the intricate workings of circRNAs, they hope to unlock its full potential as a diagnostic tool and therapeutic target for neurodegenerative disorders, paving the way for innovative treatments and better management of such devastating conditions.

Keywords: Alzheimer's disease; Circular RNAs; Neuroinflammation; Non-coding RNAs; Pathogenesis.

Publication types

Review