New preclinical biomarkers for prion diseases in the cerebrospinal fluid proteome revealed by mass spectrometry
Pérez-Lázaro, Sonia (Universidad de Zaragoza) ; Barrio, Tomás ; Bravo, Susana B. ; Sevilla, Eloisa (Universidad de Zaragoza) ; Otero, Alicia (Universidad de Zaragoza) ; Chantada-Vázquez, María del Pilar ; Martín-Burriel, Inmaculada (Universidad de Zaragoza) ; Requena, Jesús R. ; Badiola, Juan J. (Universidad de Zaragoza) ; Bolea, Rosa (Universidad de Zaragoza)
Resumen: Current diagnostic methods for prion diseases only work in late stages of the disease when neurodegeneration is irreversible. Therefore, biomarkers that can detect the disease before the onset of clinical symptoms are necessary. High-throughput discovery proteomics is of great interest in the search for such molecules. Here we used mass spectrometry to analyse the cerebrospinal fluid proteome in an animal prion disease: preclinical and clinical sheep affected with natural scrapie, and healthy sheep. Interestingly, we found 46 proteins in the preclinical stage that were significantly altered (p < 0.01) compared to healthy sheep, mainly associated with biological processes such as stress and inflammatory responses. Five of them were selected for validation by enzyme-like immunosorbent assay: synaptotagmin binding, cytoplasmic RNA interacting protein (SYNCRIP), involved in nucleic acid metabolism; phospholipase D3 (PLD3) and cathepsin D (CTSD), both related to lysosomal apoptosis; complement component 4 (C4), an element of the classical immune response; and osteopontin (SPP1), a proinflammatory cytokine. These proteins significantly increased in the preclinical stage and maintained their levels in the clinical phase, except for CTSD, whose concentration returned to basal levels in the clinical group. Further research is ongoing to explore their potential as preclinical biomarkers of prion diseases.
Idioma: Inglés
DOI: 10.1080/01652176.2024.2424837
Año: 2024
Publicado en: VETERINARY QUARTERLY 44, 1 (2024), 1-15
ISSN: 0165-2176
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2021-125398OB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RTI2018-098711-B-I00
Tipo y forma: Article (Published version)
Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)
Dataset asociado: ProteomeXchange Consortium - Mass spectrometry proteomic data ( PXD050656)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes.
Exportado de SIDERAL (2024-12-12-12:44:28)
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Idioma: Inglés
DOI: 10.1080/01652176.2024.2424837
Año: 2024
Publicado en: VETERINARY QUARTERLY 44, 1 (2024), 1-15
ISSN: 0165-2176
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2021-125398OB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RTI2018-098711-B-I00
Tipo y forma: Article (Published version)
Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)
Dataset asociado: ProteomeXchange Consortium - Mass spectrometry proteomic data ( PXD050656)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. Exportado de SIDERAL (2024-12-12-12:44:28)
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Record created 2024-12-12, last modified 2024-12-12