Vakili Omid, Asili Pooria, Babaei Zeinab, Mirahmad Maryam, Keshavarzmotamed Atoosa, Asemi Zatollah, Mafi Alireza
Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
CNS Neurol Disord Drug Targets. 2022 Aug 29. doi: 10.2174/1871527321666220829164211.
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.
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.
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.
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.
环状RNA（circRNAs）作为共价闭合的单链非编码RNA分子，最近被发现参与多种生物学过程，主要是通过靶向微小RNA。在各种神经退行性疾病（NDs）中，越来越多的证据表明circRNAs在阿尔茨海默病（AD）的发病机制中起关键作用；尽管这些RNA分子与AD进展的确切关系尚不清楚，但人们认为它们主要通过与多种蛋白质相互作用充当微小RNA海绵或基因转录调节剂，这些蛋白质参与淀粉样β（Aβ）肽以及tau蛋白的积累，而这是AD的病理标志。更有趣的是，据报道circRNAs在AD进展过程中还发挥诊断和治疗作用。
文献综述表明circRNAs对AD的发生和发展至关重要。因此，在本综述中，首先阐述circRNAs的生物合成和功能，然后全面讨论特定circRNAs与AD之间的相互作用。最后简要强调这些非编码RNA的诊断和治疗意义。
大量circRNAs在大脑中表达。因此，这些RNA分子在健康状态以及神经疾病中被视为神经功能的潜在调节因子。此外，据报道circRNAs在与最常见的神经退行性疾病AD相关方面也具有潜在的诊断和治疗能力。
已证明circRNAs可作为微小RNA的海绵，从而调节相关微小RNA的功能，包括氧化应激、神经炎症的减轻以及AD中出现的Aβ的形成和代谢。circRNAs也被提议作为在AD中具有潜在诊断能力的生物标志物。尽管具有这些特性，但将circRNAs用作治疗靶点和有前景的诊断生物标志物仍需要对这些RNA分子在AD中的功能进行进一步研究和表征。
