Department of Anatomy, Embryology and Animal Genetics, University of Zaragoza, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Agroalimentary Institute of Aragon (IA2), Institute of Health Research of Aragon (IIS), Calle Miguel Servet 13, 50013 Zaragoza, Spain.
Geriatrics Service, Hospital Nuestra Señora de Gracia, Calle Ramón y Cajal 60, 50004 Zaragoza, Spain.
Int J Mol Sci. 2020 Dec 16;21(24):9582. doi: 10.3390/ijms21249582.
Protein aggregation is classically considered the main cause of neuronal death in neurodegenerative diseases (NDDs). However, increasing evidence suggests that alteration of RNA metabolism is a key factor in the etiopathogenesis of these complex disorders. Non-coding RNAs are the major contributor to the human transcriptome and are particularly abundant in the central nervous system, where they have been proposed to be involved in the onset and development of NDDs. Interestingly, some ncRNAs (such as lncRNAs, circRNAs and pseudogenes) share a common functionality in their ability to regulate gene expression by modulating miRNAs in a phenomenon known as the competing endogenous RNA mechanism. Moreover, ncRNAs are found in body fluids where their presence and concentration could serve as potential non-invasive biomarkers of NDDs. In this review, we summarize the ceRNA networks described in Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis and spinocerebellar ataxia type 7, and discuss their potential as biomarkers of these NDDs. Although numerous studies have been carried out, further research is needed to validate these complex interactions between RNAs and the alterations in RNA editing that could provide specific ceRNET profiles for neurodegenerative disorders, paving the way to a better understanding of these diseases.
蛋白质聚集被经典地认为是神经退行性疾病（NDDs）中神经元死亡的主要原因。然而，越来越多的证据表明，RNA 代谢的改变是这些复杂疾病发病机制中的一个关键因素。非编码 RNA 是人类转录组的主要组成部分，在中枢神经系统中尤其丰富，它们被认为参与了 NDDs 的发生和发展。有趣的是，一些 ncRNA（如长链非编码 RNA、环状 RNA 和假基因）在通过调节 miRNA 来调节基因表达方面具有共同的功能，这一现象被称为竞争内源性 RNA 机制。此外，ncRNA 存在于体液中，其存在和浓度可以作为 NDD 的潜在非侵入性生物标志物。在这篇综述中，我们总结了在阿尔茨海默病、帕金森病、多发性硬化症、肌萎缩侧索硬化症和脊髓小脑共济失调 7 型中描述的 ceRNA 网络，并讨论了它们作为这些 NDD 生物标志物的潜力。尽管已经进行了许多研究，但仍需要进一步的研究来验证这些 RNA 之间的复杂相互作用以及 RNA 编辑的改变，这可能为神经退行性疾病提供特定的 ceRNET 图谱，从而更好地理解这些疾病。
