最常见的神经退行性疾病，如阿尔茨海默氏病、帕金森病和多发性硬化症的发展和恶化与COVID-19相关联。然而，COVID-19患者的神经症状和神经退行性后遗症的机制尚不清楚。中枢神经系统中基因表达和代谢产物的相互作用由miRNA驱动。这些小的非编码分子在大多数常见神经退行性疾病和COVID-19中失调。我们进行了彻底的文献筛选和数据库挖掘，以寻找SARS-CoV-2感染和神经退行性的共享miRNA景观。使用PubMed搜索COVID-19患者中差异表达的miRNA，使用Human microRNA Disease数据库搜索五种最常见的神经退行性疾病（阿尔茨海默氏病、帕金森病、亨廷顿病、肌萎缩侧索硬化症和多发性硬化症）患者的差异表达的miRNA。使用miRTarBase识别重叠miRNA的靶基因，使用Kyoto Encyclopedia of Genes and Genomes和Reactome进行通路富集分析。共发现了98种共同的miRNA。此外，其中两种（hsa-miR-34a和hsa-miR-132）被视为神经退行性的有希望的生物标志物，因为它们在所有五种最常见的神经退行性疾病和COVID-19中发生失调。此外，在四项COVID-19研究中，hsa-miR-155上调，在神经退行性过程中也发生了失调。筛选miRNA靶点识别出746个具有强烈相互作用证据的不同基因。目标富集分析强调了参与信号传导、癌症、转录和感染的最显著KEGG和Reactome通路。然而，更具体的识别通路确认了神经炎症作为共享的最重要特征。我们的通路基于方法已经确定了COVID-19和神经退行性疾病之间的重叠miRNA，这有可能为COVID-19患者的神经退行性预测提供有价值的潜力。此外，已识别的miRNA可以进一步探索为潜在的药物靶点或代理以修改共享通路中的信号传导。摘要图表确定了五种调查的神经退行性疾病和COVID-19之间共享的miRNA分子。两种重合的miRNA，hsa-miR-34a和has-miR-132，在COVID-19后可能成为神经退行性后遗症的潜在生物标志物。此外，所有五种神经退行性疾病和COVID-19之间共同的98种miRNA被鉴定出来。对共享miRNA靶基因列表执行了KEGG和Reactome通路富集分析，并最终评估了前20个通路用于发现新的药物靶点的潜力。确定的重叠miRNA和通路的共同特征是神经炎症。AD，阿尔茨海默氏病；ALS，肌萎缩侧索硬化症；COVID-19，2019年冠状病毒病；HD，亨廷顿病；KEGG，Kyoto Encyclopedia of Genes and Genomes；MS，多发性硬化症；PD，帕金森病。版权所有©2023 Redenšek Trampuž，Vogrinc，Goričar和Dolžan。

Development and worsening of most common neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, have been associated with COVID-19 However, the mechanisms associated with neurological symptoms in COVID-19 patients and neurodegenerative sequelae are not clear. The interplay between gene expression and metabolite production in CNS is driven by miRNAs. These small non-coding molecules are dysregulated in most common neurodegenerative diseases and COVID-19.We have performed a thorough literature screening and database mining to search for shared miRNA landscapes of SARS-CoV-2 infection and neurodegeneration. Differentially expressed miRNAs in COVID-19 patients were searched using PubMed, while differentially expressed miRNAs in patients with five most common neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis) were searched using the Human microRNA Disease Database. Target genes of the overlapping miRNAs, identified with the miRTarBase, were used for the pathway enrichment analysis performed with Kyoto Encyclopedia of Genes and Genomes and Reactome.In total, 98 common miRNAs were found. Additionally, two of them (hsa-miR-34a and hsa-miR-132) were highlighted as promising biomarkers of neurodegeneration, as they are dysregulated in all five most common neurodegenerative diseases and COVID-19. Additionally, hsa-miR-155 was upregulated in four COVID-19 studies and found to be dysregulated in neurodegeneration processes as well. Screening for miRNA targets identified 746 unique genes with strong evidence for interaction. Target enrichment analysis highlighted most significant KEGG and Reactome pathways being involved in signaling, cancer, transcription and infection. However, the more specific identified pathways confirmed neuroinflammation as being the most important shared feature.Our pathway based approach has identified overlapping miRNAs in COVID-19 and neurodegenerative diseases that may have a valuable potential for neurodegeneration prediction in COVID-19 patients. Additionally, identified miRNAs can be further explored as potential drug targets or agents to modify signaling in shared pathways. Graphical AbstractShared miRNA molecules among the five investigated neurodegenerative diseases and COVID-19 were identified. The two overlapping miRNAs, hsa-miR-34a and has-miR-132, present potential biomarkers of neurodegenerative sequelae after COVID-19. Furthermore, 98 common miRNAs between all five neurodegenerative diseases together and COVID-19 were identified. A KEGG and Reactome pathway enrichment analyses was performed on the list of shared miRNA target genes and finally top 20 pathways were evaluated for their potential for identification of new drug targets. A common feature of identified overlapping miRNAs and pathways is neuroinflammation. AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; COVID-19, coronavirus disease 2019; HD, Huntington's disease; KEGG, Kyoto Encyclopedia of Genes and Genomes; MS, multiple sclerosis; PD, Parkinson's disease.Copyright © 2023 Redenšek Trampuž, Vogrinc, Goričar and Dolžan.