Shared miRNA landscapes of COVID-19 and neurodegeneration confirm neuroinflammation as an important overlapping feature

Redenšek Trampuž, Sara (author), Vogrinc, David (author), Goričar, Katja (author), Dolžan, Vita (author)

Introduction: 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. Methods: 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. Results: 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. Discussion: 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.

• Language: English
• Keywords: COVID-19, neurodegeneration, Alzheimer’s disease, neuroinflammation, Parkinson’s disease, miRNA, biomarker
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 24 str.
• Numbering: Vol. 16, art. 1123955
• PID: 20.500.12556/RUL-153998
• UDC: 616.9
• ISSN on article: 1662-5099
• DOI: 10.3389/fnmol.2023.1123955
• COBISS.SI-ID: 146233091
• Publication date in RUL: 18.01.2024

Record is a part of a journal

• Title: Frontiers in molecular neuroscience
• Shortened title: Front. mol. neurosci.
• Publisher: Frontiers Media
• ISSN: 1662-5099
• COBISS.SI-ID: 5029402

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: COVID-19, nevrodegeneracija, Alzheimerjeva bolezen

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0170
• Name: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku