环状rna——人类神经系统疾病分子机制的现代观点。寻找新的治疗药物的前景

P. Shabanov, V. I. Vashchenko, L. Savelieva, Yuliia E. Romashova
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引用次数: 0

摘要

在哺乳动物中,许多种类的非编码rna (ncRNAs)在大脑中的表达水平比在其他器官中要高得多。最近的研究发现了一类新的ncRNAs,称为环状rna (circRNAs),它是通过外显子、内含子或外显子-内含子的反剪接和融合形成共价闭环而产生的。circrna在大脑中也高度富集,并且从胚胎到成年阶段不断增加。尽管circRNAs的功能意义和作用机制仍在积极探索中,但它们被认为可以调节宿主基因的转录和microrna和RNA结合蛋白的分离。一些环状rna也被证明具有翻译形成多肽的潜力。环状rna的表达和丰度在正常大脑中似乎是时空维持的。circRNAs表达的改变也被认为通过影响血管生成、神经元可塑性、自噬、细胞凋亡和炎症等机制介导多种疾病,包括脑肿瘤生长、急性和慢性神经退行性疾病。这些非凡的特性使得环状rna可能适合作为有前途的分子生物标志物,特别是神经退行性疾病。这篇综述概述了关于环状rna的新数据,强调了它们在基本神经退行性疾病发病机制中的作用:强调了它们在主要神经退行性疾病、阿尔茨海默病、额颞叶痴呆、帕金森病、精神分裂症、ALS发病机制中的作用,并展望了它们在生物标志物搜索中的潜在用途。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circular RNAs - modern view on the molecular mechanism of neurologic diseases of the human. Prospects of search of new therapeutic agents
In mammals, many classes of noncoding RNAs (ncRNAs) are expressed at a much higher level in the brain than in other organs. Recent studies have identified a new class of ncRNAs called circular RNAs (circRNAs), which are produced by back-splicing and fusion of either exons, introns, or both exon-intron into covalently closed loops. The circRNAs are also highly enriched in the brain and increase continuously from the embryonic to the adult stage.Although the functional significance and mechanism of action of circRNAs are still being actively explored, they are thought to regulate the transcription of their host genes and sequestration of miRNAs and RNA binding proteins. Some circRNAs are also shown to have translation potential to form peptides. The expression and abundance of circRNAs seem to be spatiotemporally maintained in a normal brain.Altered expression of circRNAs is also thought to mediate several disorders, including brain-tumor growth, and acute and chronic neurodegenerative disorders by affecting mechanisms such as angiogenesis, neuronal plasticity, autophagy, apoptosis, and inflammation. These extraordinary peculiarities make circRNAs potentially suitable as promising molecular biomarkers, especially of neurodegenerative diseases. This review represents generalisation of the new data about circRNAs, underlining their role in a pathogenesis of the basic neurodegenerative disorders: emphasizing their role in pathogenesis of major neurodegenerative disorders, Alzheimers disease, frontotemporal dementia, and Parkinsons diseases, schizophrenia diseases, ALS with a look toward their potential usefulness in biomarker searching.
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