dc.contributor.author | Quintela López, Tania | |
dc.contributor.author | Ortiz Sanz, Carolina | |
dc.contributor.author | Serrano Regal, María Paz | |
dc.contributor.author | Gaminde Blasco, Adhara Mikaela | |
dc.contributor.author | Valero Gómez-Lobo, Jorge | |
dc.contributor.author | Baleriola, Jimena | |
dc.contributor.author | Sánchez Gómez, María Victoria ![ORCID](/themes/Mirage2//images/orcid_16x16.png) | |
dc.contributor.author | Matute Almau, Carlos José | |
dc.contributor.author | Alberdi Alfonso, Elena María ![ORCID](/themes/Mirage2//images/orcid_16x16.png) | |
dc.date.accessioned | 2020-02-25T09:20:27Z | |
dc.date.available | 2020-02-25T09:20:27Z | |
dc.date.issued | 2019-06-06 | |
dc.identifier.citation | Cell Death & Disease 10 : (2019) // Article ID UNSP 445 | es_ES |
dc.identifier.issn | 2041-4889 | |
dc.identifier.uri | http://hdl.handle.net/10810/41430 | |
dc.description.abstract | Alzheimer's disease (AD) is characterized by a progressive cognitive decline that correlates with the levels of amyloid beta-peptide (A beta) oligomers. Strong evidences connect changes of oligodendrocyte function with the onset of neurodegeneration in AD. However, the mechanisms controlling oligodendrocyte responses to A beta are still elusive. Here, we tested the role of A beta in oligodendrocyte differentiation, maturation, and survival in isolated oligodendrocytes and in organotypic cerebellar slices. We found that A beta peptides specifically induced local translation of 18.5-kDa myelin basic protein (MBP) isoform in distal cell processes concomitant with an increase of process complexity of MBPexpressing oligodendrocytes. A beta oligomers required integrin beta 1 receptor, Src-family kinase Fyn and Ca2+/CaMKII as effectors to modulate MBP protein expression. The pharmacological inhibition of Fyn kinase also attenuated oligodendrocyte differentiation and survival induced by A beta oligomers. Similarly, using ex vivo organotypic cerebellar slices A beta promoted MBP upregulation through Fyn kinase, and modulated oligodendrocyte population dynamics by inducing cell proliferation and differentiation. Importantly, application of A beta to cerebellar organotypic slices enhanced remyelination and oligodendrocyte lineage recovery in lysolecithin (LPC)-induced demyelination. These data reveal an important role of A beta in oligodendrocyte lineage function and maturation, which may be relevant to AD pathogenesis. | es_ES |
dc.description.sponsorship | This study was supported by the Basque Government (fellowship to T.Q.-L.), University of the Basque Country (UPV/EHU; fellowship to C.O.-S.), CIBERNED and MINECO (fellowship to A.G.-B. FPU17/04891; M.P.S.-R. SAF2013-45084-R and SAF2016-75292-R). We thank S. Marcos, A. Martinez, and L. Escobar for technical assistance. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/FPU17/04891 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2013-45084-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2016-75292-R | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | myelin basic-protein | es_ES |
dc.subject | alzheimers-disease | es_ES |
dc.subject | amyloid hypothesis | es_ES |
dc.subject | cns myelination | es_ES |
dc.subject | cell-survival | es_ES |
dc.subject | white-matter | es_ES |
dc.subject | mice | es_ES |
dc.subject | demyelination | es_ES |
dc.subject | association | es_ES |
dc.subject | activation | es_ES |
dc.title | A beta oligomers promote oligodendrocyte differentiation and maturation via integrin beta 1 and Fyn kinase signaling | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This article is licensed under a Creative Commons Attribution 4.0 International License. (CC BY 4.0) | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.nature.com/articles/s41419-019-1636-8 | es_ES |
dc.identifier.doi | 10.1038/s41419-019-1636-8 | |
dc.departamentoes | Neurociencias | es_ES |
dc.departamentoeu | Neurozientziak | es_ES |