Recombinant Integrin β1 Signal Peptide Blocks Gliosis Induced by Aβ Oligomers
dc.contributor.author | Ortiz Sanz, Carolina | |
dc.contributor.author | Llavero Bernal, Francisco | |
dc.contributor.author | Zuazo Ibarra, Jone | |
dc.contributor.author | Balantzategi Fernández de Arroiabe, Uxue | |
dc.contributor.author | Quintela López, Tania | |
dc.contributor.author | Wyssenbach Ibarra, Ane | |
dc.contributor.author | Capetillo González de Zarate, Estibaliz | |
dc.contributor.author | Matute Almau, Carlos José | |
dc.contributor.author | Alberdi Alfonso, Elena María ![]() | |
dc.contributor.author | Zugaza Gurruchaga, José Luis ![]() | |
dc.date.accessioned | 2022-05-31T11:18:49Z | |
dc.date.available | 2022-05-31T11:18:49Z | |
dc.date.issued | 2022-05-20 | |
dc.identifier.citation | International Journal of Molecular Sciences 23(10) : (2022) // Article ID 5747 | es_ES |
dc.identifier.issn | 1422-0067 | |
dc.identifier.uri | http://hdl.handle.net/10810/56806 | |
dc.description.abstract | Glial cells participate actively in the early cognitive decline in Alzheimer’s disease (AD) pathology. In fact, recent studies have found molecular and functional abnormalities in astrocytes and microglia in both animal models and brains of patients suffering from this pathology. In this regard, reactive gliosis intimately associated with amyloid plaques has become a pathological hallmark of AD. A recent study from our laboratory reports that astrocyte reactivity is caused by a direct interaction between amyloid beta (Aβ) oligomers and integrin β1. Here, we have generated four recombinant peptides including the extracellular domain of integrin β1, and evaluated their capacity both to bind in vitro to Aβ oligomers and to prevent in vivo Aβ oligomer-induced gliosis and endoplasmic reticulum stress. We have identified the minimal region of integrin β1 that binds to Aβ oligomers. This region is called signal peptide and corresponds to the first 20 amino acids of the integrin β1 N-terminal domain. This recombinant integrin β1 signal peptide prevented Aβ oligomer-induced ROS generation in primary astrocyte cultures. Furthermore, we carried out intrahippocampal injection in adult mice of recombinant integrin β1 signal peptide combined with or without Aβ oligomers and we evaluated by immunohistochemistry both astrogliosis and microgliosis as well as endoplasmic reticulum stress. The results show that recombinant integrin β1 signal peptide precluded both astrogliosis and microgliosis and endoplasmic reticulum stress mediated by Aβ oligomers in vivo. We have developed a molecular tool that blocks the activation of the molecular cascade that mediates gliosis via Aβ oligomer/integrin β1 signaling. | es_ES |
dc.description.sponsorship | E.A. was supported by MICINN (PID2019-108465RB-I00) and Basque Government (PIBA_2020_1_0012). C.M. was supported by MICINN (PID2019-109724RB-I00), Basque Government (IT1203-19) and CIBERNED (CB06/0005/0076). E.C.-Z. was supported by Basque Government (ELKARTEK KK-2020/00034; PIBA_2016_1_0009). J.L.Z. was supported by the Instituto de Salud Carlos III (PI18/00207), Basque Government (PIBA_2020_1_0048) and University of Basque Country Grant (US19/04). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2019-108465RB-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2019-109724RB-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | |
dc.subject | Aβ oligomers | es_ES |
dc.subject | integrin β1 | es_ES |
dc.subject | interactive region | es_ES |
dc.subject | astrogliosis | es_ES |
dc.subject | microgliosis | es_ES |
dc.subject | interferent peptides | es_ES |
dc.title | Recombinant Integrin β1 Signal Peptide Blocks Gliosis Induced by Aβ Oligomers | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2022-05-27T13:37:14Z | |
dc.rights.holder | 2022 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 (https://creativecommons.org/licenses/by/4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/1422-0067/23/10/5747/htm | es_ES |
dc.identifier.doi | 10.3390/ijms23105747 | |
dc.departamentoes | Neurociencias | |
dc.departamentoes | Genética, antropología física y fisiología animal | |
dc.departamentoeu | Neurozientziak | |
dc.departamentoeu | Genetika,antropologia fisikoa eta animalien fisiologia |
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Except where otherwise noted, this item's license is described as 2022 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 (https://creativecommons.org/licenses/by/4.0/).