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http://hdl.handle.net/10261/217771
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Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | López-Font, Inmaculada | es_ES |
dc.contributor.author | Sogorb-Esteve, Aitana | es_ES |
dc.contributor.author | Javier-Torrent, Míriam | es_ES |
dc.contributor.author | Brinkmalm, Gunnar | es_ES |
dc.contributor.author | Herrando-Grabulosa, Mireia | es_ES |
dc.contributor.author | García-Lareu, Belen | es_ES |
dc.contributor.author | Turon-Sans, Janina | es_ES |
dc.contributor.author | Rojas-García, Ricardo | es_ES |
dc.contributor.author | Lleó, Alberto | es_ES |
dc.contributor.author | Saura, Carlos A. | es_ES |
dc.contributor.author | Zetterberg, Henrik | es_ES |
dc.contributor.author | Blennow, Kaj | es_ES |
dc.contributor.author | Bosch, Assumpció | es_ES |
dc.contributor.author | Navarro, Xavier | es_ES |
dc.contributor.author | Sáez-Valero, Javier | es_ES |
dc.date.accessioned | 2020-08-11T11:48:11Z | - |
dc.date.available | 2020-08-11T11:48:11Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Neurobiology of Disease 124: 428-438 (2019) | es_ES |
dc.identifier.issn | 0969-9961 | - |
dc.identifier.uri | http://hdl.handle.net/10261/217771 | - |
dc.description.abstract | ErbB4 is a transmembrane receptor tyrosine kinase that binds to neuregulins to activate signaling. Proteolytic cleavage of ErbB4 results in release of soluble fragments of ErbB4 into the interstitial fluid. Disruption of the neuregulin-ErbB4 pathway has been suggested to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). This study assesses whether soluble proteolytic fragments of the ErbB4 ectodomain (ecto-ErbB4) can be detected in cerebrospinal fluid (CSF) and plasma, and if the levels are altered in ALS. Immunoprecipitation combined with mass spectrometry or western blotting analyses confirmed the presence of ecto-ErbB4 in human CSF. Several anti-ErbB4-reactive bands, including a 55 kDa fragment, were detected in CSF. The bands were generated in the presence of neuregulin-1 (Nrg1) and were absent in plasma from ErbB4 knockout mice. Ecto-ErbB4 levels were decreased in CSF from ALS patients (n = 20) and ALS with concomitant frontotemporal dementia patients (n = 10), compared to age-matched controls (n = 13). A similar decrease was found for the short ecto-ErbB4 fragments in plasma of the same subjects. Likewise, the 55-kDa ecto-ErbB4 fragments were decreased in the plasma of the two transgenic mouse models of ALS (SOD1G93A and TDP-43A315T). Intracellular ErbB4 fragments were decreased in the frontal cortex from SOD1G93A mice, indicating a reduction in Nrg-dependent induction of ErbB4 proteolytic processing, and suggesting impaired signaling. Accordingly, overexpression of Nrg1 induced by an adeno-associated viral vector increased the levels of the ecto-ErbB4 fragment in the SOD1G93A mice. We conclude that the determination of circulating ecto-ErbB4 fragments could be a tool to evaluate the impairment of the ErbB4 pathway and may be a useful biomarker in ALS. | es_ES |
dc.description.sponsorship | This work was supported by grants from the Fondo de Investigaciones Sanitarias (PI15/00665 to JSV and PI15/01618 to RRG), cooperative project 2015-01 from CIBERNED (Instituto de Salud Carlos III, Spain) to XN and JSV, all co-funded by the Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, “Una manera de hacer Europa”; grants TV3201428-10 to XN and 201437 to RRG of Fundació La Marato-TV3; and grant #20289 of AFM-Telethon to XN. HZ is a Wallenberg Academy Fellow and is supported by grants from the Swedish and European Research Councils and the UK Dementia Research Institute at UCL. KB holds the Torsten Söderberg Professorship in Medicine at the Royal Swedish Academy of Sciences. We also acknowledge financial support from the Spanish Ministerio de Economía y Competitividad, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2017-0723). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.relation | info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/SEV-2017-0723 | es_ES |
dc.relation | SEV-2017-0723/AEI/10.13039/501100011033 | es_ES |
dc.rights | closedAccess | es_ES |
dc.subject | Amyotrophic lateral sclerosis | es_ES |
dc.subject | ErbB4 | es_ES |
dc.subject | Biomarkers | es_ES |
dc.subject | Cerebrospinal fluid | es_ES |
dc.subject | Brain | es_ES |
dc.subject | Plasma | es_ES |
dc.title | Decreased circulating ErbB4 ectodomain fragments as a read-out of impaired signaling function in amyotrophic lateral sclerosis | es_ES |
dc.type | artículo | es_ES |
dc.identifier.doi | 10.1016/j.nbd.2018.12.021 | - |
dc.description.peerreviewed | Peer reviewed | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.nbd.2018.12.021 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | European Commission | es_ES |
dc.contributor.funder | Fundació La Marató de TV3 | es_ES |
dc.contributor.funder | Wallenberg Academy | es_ES |
dc.contributor.funder | Swedish Research Council | es_ES |
dc.contributor.funder | Torsten Söderberg Foundation | es_ES |
dc.contributor.funder | Royal Swedish Academy of Sciences | es_ES |
dc.contributor.funder | Agencia Estatal de Investigación (España) | es_ES |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | es_ES |
dc.relation.csic | Sí | es_ES |
oprm.item.hasRevision | no ko 0 false | * |
dc.identifier.funder | http://dx.doi.org/10.13039/501100011033 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100004587 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003329 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100001725 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/100007464 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100000780 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/100008666 | es_ES |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.languageiso639-1 | en | - |
item.fulltext | No Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | none | - |
item.openairetype | artículo | - |
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