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Aβ oligomers promote oligodendrocyte differentiation and maturation via integrin β1 and Fyn kinase signaling

Alzheimer´s disease (AD) is characterized by a progressive cognitive decline that correlates with the levels of amyloid β-peptide (Aβ) oligomers. Strong evidences connect changes of oligodendrocyte function with the onset of neurodegeneration in AD. However, the mechanisms controlling oligodendrocyt...

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Autores principales: Quintela-López, Tania, Ortiz-Sanz, Carolina, Serrano-Regal, Mari Paz, Gaminde-Blasco, Adhara, Valero, Jorge, Baleriola, Jimena, Sánchez-Gómez, Maria Victoria, Matute, Carlos, Alberdi, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554322/
https://www.ncbi.nlm.nih.gov/pubmed/31171765
http://dx.doi.org/10.1038/s41419-019-1636-8
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author Quintela-López, Tania
Ortiz-Sanz, Carolina
Serrano-Regal, Mari Paz
Gaminde-Blasco, Adhara
Valero, Jorge
Baleriola, Jimena
Sánchez-Gómez, Maria Victoria
Matute, Carlos
Alberdi, Elena
author_facet Quintela-López, Tania
Ortiz-Sanz, Carolina
Serrano-Regal, Mari Paz
Gaminde-Blasco, Adhara
Valero, Jorge
Baleriola, Jimena
Sánchez-Gómez, Maria Victoria
Matute, Carlos
Alberdi, Elena
author_sort Quintela-López, Tania
collection PubMed
description Alzheimer´s disease (AD) is characterized by a progressive cognitive decline that correlates with the levels of amyloid β-peptide (Aβ) oligomers. Strong evidences connect changes of oligodendrocyte function with the onset of neurodegeneration in AD. However, the mechanisms controlling oligodendrocyte responses to Aβ are still elusive. Here, we tested the role of Aβ in oligodendrocyte differentiation, maturation, and survival in isolated oligodendrocytes and in organotypic cerebellar slices. We found that Aβ 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 MBP-expressing oligodendrocytes. Aβ oligomers required integrin β1 receptor, Src-family kinase Fyn and Ca(2+)/CaMKII as effectors to modulate MBP protein expression. The pharmacological inhibition of Fyn kinase also attenuated oligodendrocyte differentiation and survival induced by Aβ oligomers. Similarly, using ex vivo organotypic cerebellar slices Aβ promoted MBP upregulation through Fyn kinase, and modulated oligodendrocyte population dynamics by inducing cell proliferation and differentiation. Importantly, application of Aβ to cerebellar organotypic slices enhanced remyelination and oligodendrocyte lineage recovery in lysolecithin (LPC)-induced demyelination. These data reveal an important role of Aβ in oligodendrocyte lineage function and maturation, which may be relevant to AD pathogenesis.
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spelling pubmed-65543222019-06-17 Aβ oligomers promote oligodendrocyte differentiation and maturation via integrin β1 and Fyn kinase signaling Quintela-López, Tania Ortiz-Sanz, Carolina Serrano-Regal, Mari Paz Gaminde-Blasco, Adhara Valero, Jorge Baleriola, Jimena Sánchez-Gómez, Maria Victoria Matute, Carlos Alberdi, Elena Cell Death Dis Article Alzheimer´s disease (AD) is characterized by a progressive cognitive decline that correlates with the levels of amyloid β-peptide (Aβ) oligomers. Strong evidences connect changes of oligodendrocyte function with the onset of neurodegeneration in AD. However, the mechanisms controlling oligodendrocyte responses to Aβ are still elusive. Here, we tested the role of Aβ in oligodendrocyte differentiation, maturation, and survival in isolated oligodendrocytes and in organotypic cerebellar slices. We found that Aβ 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 MBP-expressing oligodendrocytes. Aβ oligomers required integrin β1 receptor, Src-family kinase Fyn and Ca(2+)/CaMKII as effectors to modulate MBP protein expression. The pharmacological inhibition of Fyn kinase also attenuated oligodendrocyte differentiation and survival induced by Aβ oligomers. Similarly, using ex vivo organotypic cerebellar slices Aβ promoted MBP upregulation through Fyn kinase, and modulated oligodendrocyte population dynamics by inducing cell proliferation and differentiation. Importantly, application of Aβ to cerebellar organotypic slices enhanced remyelination and oligodendrocyte lineage recovery in lysolecithin (LPC)-induced demyelination. These data reveal an important role of Aβ in oligodendrocyte lineage function and maturation, which may be relevant to AD pathogenesis. Nature Publishing Group UK 2019-06-06 /pmc/articles/PMC6554322/ /pubmed/31171765 http://dx.doi.org/10.1038/s41419-019-1636-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Quintela-López, Tania
Ortiz-Sanz, Carolina
Serrano-Regal, Mari Paz
Gaminde-Blasco, Adhara
Valero, Jorge
Baleriola, Jimena
Sánchez-Gómez, Maria Victoria
Matute, Carlos
Alberdi, Elena
Aβ oligomers promote oligodendrocyte differentiation and maturation via integrin β1 and Fyn kinase signaling
title Aβ oligomers promote oligodendrocyte differentiation and maturation via integrin β1 and Fyn kinase signaling
title_full Aβ oligomers promote oligodendrocyte differentiation and maturation via integrin β1 and Fyn kinase signaling
title_fullStr Aβ oligomers promote oligodendrocyte differentiation and maturation via integrin β1 and Fyn kinase signaling
title_full_unstemmed Aβ oligomers promote oligodendrocyte differentiation and maturation via integrin β1 and Fyn kinase signaling
title_short Aβ oligomers promote oligodendrocyte differentiation and maturation via integrin β1 and Fyn kinase signaling
title_sort aβ oligomers promote oligodendrocyte differentiation and maturation via integrin β1 and fyn kinase signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554322/
https://www.ncbi.nlm.nih.gov/pubmed/31171765
http://dx.doi.org/10.1038/s41419-019-1636-8
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