Dysregulated microRNAs in blood correlate with central nervous system neuropathology of prion disease

The role of microRNAs (miRNAs) in neurodegenerative diseases has gained significant attention because of their involvement in gene regulation and potential as biomarkers. In prion diseases, including scrapie, miRNAs may modulate pathogenesis and disease progression. This study investigated circulati...

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Detalles Bibliográficos
Autores: Pérez-Lázaro, Sonia, Martín-Burriel, Inmaculada, Cozzuto, Luca, Ponomarenko, Julia, Badiola, Juan J., Bolea, Rosa, Toivonen, Janne M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/71445
Acceso en línea:http://hdl.handle.net/10230/71445
http://dx.doi.org/10.1186/s13567-025-01566-0
Access Level:acceso abierto
Palabra clave:Prion
Biomarkers
microRNA
Neurodegenerative diseases
Scrapie
Descripción
Sumario:The role of microRNAs (miRNAs) in neurodegenerative diseases has gained significant attention because of their involvement in gene regulation and potential as biomarkers. In prion diseases, including scrapie, miRNAs may modulate pathogenesis and disease progression. This study investigated circulating miRNA profiles in the blood of sheep naturally affected by scrapie at preclinical and clinical stages using small RNA sequencing and RT-qPCR validation. While only one novel miRNA was dysregulated in preclinical blood samples, 66 previously annotated miRNAs were significantly dysregulated in clinical sheep compared with healthy sheep. These miRNAs are associated with pathways commonly altered in neurodegenerative diseases, such as autophagy, ubiquitin-mediated proteolysis, and endoplasmic reticulum protein processing. Notably, miR-1271-5p, let-7f-5p, miR-186-5p, and miR-425-5p were consistently upregulated in the central nervous system of clinical animals, replicating the results observed in blood, with an increasing trend already in the preclinical stage and a strong correlation with neuropathological prion features. Additionally, predicted target genes such as UBQLN2, PGK1, KRAS, and CLTC were inversely expressed relative to these miRNAs, supporting their regulatory roles. These findings highlight the relevance of circulating miRNAs in prion neuropathology and support further research into the specific functional roles of these miRNAs and their predictive capacity for disease progression.