Increased C-X-C motif chemokine ligand 12 levels in cerebrospinal fluid as a candidate biomarker in sporadic amyotrophic lateral sclerosis

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dc.contributor.authorAndrés Benito, Pol
dc.contributor.authorPovedano, Mónica
dc.contributor.authorDomínguez Rubio, Raúl
dc.contributor.authorMarco, Carla
dc.contributor.authorColomina, María J.
dc.contributor.authorLópez-Pérez, Óscar
dc.contributor.authorSantana, Isabel
dc.contributor.authorBaldeiras, Inês
dc.contributor.authorMartínez-Yelámos, Sergio
dc.contributor.authorZerr, Inga
dc.contributor.authorLlorens, Franc
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.authorSantamaría Martínez, Enrique
dc.contributor.authorFerrer, Isidro
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2021-06-25T12:34:24Z
dc.date.available2021-06-25T12:34:24Z
dc.date.issued2020
dc.description.abstractSporadic amyotrophic lateral sclerosis (sALS) is a fatal progressive neurodegenerative disease affecting upper and lower motor neurons. Biomarkers are useful to facilitate the diagnosis and/or prognosis of patients and to reveal possible mechanistic clues about the disease. This study aimed to identify and validate selected putative biomarkers in the cerebrospinal fluid (CSF) of sALS patients at early disease stages compared with age-matched controls and with other neurodegenerative diseases including Alzheimer disease (AD), spinal muscular atrophy type III (SMA), frontotemporal dementia behavioral variant (FTD), and multiple sclerosis (MS). SWATH acquisition on liquid chromatography-tandem mass spectrometry (LC–MS/MS) for protein quantitation, and ELISA for validation, were used in CSF samples of sALS cases at early stages of the disease. Analysis of mRNA and protein expression was carried out in the anterior horn of the lumbar spinal cord in post-mortem tissue of sALS cases (terminal stage) and controls using RTq-PCR, and Western blotting, and immunohistochemistry, respectively. SWATH acquisition on liquid chromatography-tandem mass spectrometry (LC–MS/MS) revealed 51 differentially expressed proteins in the CSF in sALS. Receiver operating characteristic (ROC) curves showed CXCL12 to be the most valuable candidate biomarker. We validated the values of CXCL12 in CSF with ELISA in two different cohorts. Besides sALS, increased CXCL12 levels were found in MS but were not altered in AD, SMA, and FTD. Therefore, increased CXCL12 levels in the CSF can be useful in the diagnoses of MS and sALS in the context of the clinical settings. CXCL12 immunoreactivity was localized in motor neurons in control and sALS, and in a few glial cells in sALS at the terminal stage; CXCR4 was in a subset of oligodendroglial-like cells and axonal ballooning of motor neurons in sALS; and CXCR7 in motor neurons in control and sALS, and reactive astrocytes in the pyramidal tracts in terminal sALS. CXCL12/CXCR4/CXCR7 axis in the spinal cord probably plays a complex role in inflammation, oligodendroglial and astrocyte signaling, and neuronal and axonal preservation in sALS.en
dc.description.sponsorshipThe project leading to these results received funding from Fundació Miquel Valls, 'Retos todos unidos contra la ELA' and 'Proyecto DGeneracion conexiones con sentido' to MP. The study was also supported by the Ministry of Economy and Competitiveness, Institute of Health Carlos III (ISCIII) (co-funded by European RegiSonal Development Fund, ERDF, a way to build Europe): FISPI17/000809 to IF; and FIS (ISCIII) grant PI19/00144 to FLl. The Proteomics Unit of Navarrabiomed is supported by grant PT17/0019/009 to JFI, of the PE I+D+I 2013-2016 funded by ISCIII and FEDER. Part of this work was funded by a grant from the Spanish Ministry of Science Innovation and Universities (Ref. PID2019-110356RB-I00) to JFI and ES.en
dc.format.extent21 p.
dc.format.mimetypeapplication/pdfen
dc.identifier.doi10.3390/ijms21228680
dc.identifier.issn1661-6596
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/40057
dc.language.isoengen
dc.publisherMDPIen
dc.relation.ispartofInternational Journal of Molecular Sciences, 2020, 21, 8680en
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/PT17%2F0019%2F009/
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110356RB-I00/ES/
dc.relation.publisherversionhttps://doi.org/10.3390/ijms21228680
dc.rights© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAAASen
dc.subjectAmyotrophic lateral sclerosisen
dc.subjectBiomarkersen
dc.subjectCerebrospinal fluiden
dc.subjectCXCL12en
dc.subjectCXCR4en
dc.subjectCXCR7en
dc.subjectProteomicsen
dc.subjectS1006Aen
dc.titleIncreased C-X-C motif chemokine ligand 12 levels in cerebrospinal fluid as a candidate biomarker in sporadic amyotrophic lateral sclerosisen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublication86d1b76e-4790-40b1-a3ec-72331c5c6199
relation.isAuthorOfPublicationabacfd17-2b93-4d99-bae2-52053d57401e
relation.isAuthorOfPublication.latestForDiscovery86d1b76e-4790-40b1-a3ec-72331c5c6199

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