Amyloid β1–42 Oligomers Induce Galectin–1S8 O–GlcNAcylation Leading to Microglia Migration

Protein O–GlcNAcylation has been associated with neurodegenerative diseases such as Alzheimer’s disease (AD). The O–GlcNAcylation of the Amyloid Precursor Protein (APP) regulates both the trafficking and the processing of the APP through the amyloidogenic pathway, resulting in the release and aggreg...

ver descrição completa

Detalhes bibliográficos
Autores: Arrazola Sastre, Alazne, Luque Montoro, Miriam, Llavero Bernal, Francisco, Zugaza Gurruchaga, José Luis
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/62085
Acesso em linha:http://hdl.handle.net/10810/62085
Access Level:acceso abierto
Palavra-chave:amyloid β1–42 oligomers
OGT
O-GlcNAcylation
Galectin–1
Galectin–1Serine 8–O–GlcNAcylation
Gal–1S8A
microglia
migration
id ES_d0ecbdbc2a12e9ff6715736fab360868
oai_identifier_str oai:addi.ehu.eus:10810/62085
network_acronym_str ES
network_name_str España
repository_id_str
spelling Amyloid β1–42 Oligomers Induce Galectin–1S8 O–GlcNAcylation Leading to Microglia MigrationArrazola Sastre, AlazneLuque Montoro, MiriamLlavero Bernal, FranciscoZugaza Gurruchaga, José Luisamyloid β1–42 oligomersOGTO-GlcNAcylationGalectin–1Galectin–1Serine 8–O–GlcNAcylationGal–1S8AmicrogliamigrationProtein O–GlcNAcylation has been associated with neurodegenerative diseases such as Alzheimer’s disease (AD). The O–GlcNAcylation of the Amyloid Precursor Protein (APP) regulates both the trafficking and the processing of the APP through the amyloidogenic pathway, resulting in the release and aggregation of the Aβ1–42 peptide. Microglia clears Aβ aggregates and dead cells to maintain brain homeostasis. Here, using LC-MS/MS, we revealed that the Aβ1–42 oligomers modify the microglia O-GlcNAcome. We identified 55 proteins, focusing our research on Galectin-1 protein since it is a very versatile protein from a functional point of view. Combining biochemical with genetic approaches, we demonstrated that Aβ1–42 oligomers specifically target Galectin–1S8 O–GlcNAcylation via OGT. In addition to this, the Gal–1–O–GlcNAcylated form, in turn, controls human microglia migration. Given the importance of microglia migration in the progression of AD, this study reports the relationship between the Aβ1–42 oligomers and Serine 8–O–GlcNAcylation of Galectin–1 to drive microglial migration.A.A.S. received a predoctoral fellowship (PRE_2017_1_0016) from the Basque Government. M.L.M. received a fellowship from the Foundation “Jesús de Gangoiti y Barrera”. J.L.Z. is supported by the Instituto de Salud Carlos III (PI18/00207), Basque Government (PIBA_2020_1_0048 and Elkartek Program KK-2023/00050) and University of Basque Country Grant (US19/04).MDPI2023202320232023info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/62085reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.mdpi.com/2073-4409/12/14/1876info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/© 2023 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/).oai:addi.ehu.eus:10810/620852026-06-18T09:23:17Z
dc.title.none.fl_str_mv Amyloid β1–42 Oligomers Induce Galectin–1S8 O–GlcNAcylation Leading to Microglia Migration
title Amyloid β1–42 Oligomers Induce Galectin–1S8 O–GlcNAcylation Leading to Microglia Migration
spellingShingle Amyloid β1–42 Oligomers Induce Galectin–1S8 O–GlcNAcylation Leading to Microglia Migration
Arrazola Sastre, Alazne
amyloid β1–42 oligomers
OGT
O-GlcNAcylation
Galectin–1
Galectin–1Serine 8–O–GlcNAcylation
Gal–1S8A
microglia
migration
title_short Amyloid β1–42 Oligomers Induce Galectin–1S8 O–GlcNAcylation Leading to Microglia Migration
title_full Amyloid β1–42 Oligomers Induce Galectin–1S8 O–GlcNAcylation Leading to Microglia Migration
title_fullStr Amyloid β1–42 Oligomers Induce Galectin–1S8 O–GlcNAcylation Leading to Microglia Migration
title_full_unstemmed Amyloid β1–42 Oligomers Induce Galectin–1S8 O–GlcNAcylation Leading to Microglia Migration
title_sort Amyloid β1–42 Oligomers Induce Galectin–1S8 O–GlcNAcylation Leading to Microglia Migration
dc.creator.none.fl_str_mv Arrazola Sastre, Alazne
Luque Montoro, Miriam
Llavero Bernal, Francisco
Zugaza Gurruchaga, José Luis
author Arrazola Sastre, Alazne
author_facet Arrazola Sastre, Alazne
Luque Montoro, Miriam
Llavero Bernal, Francisco
Zugaza Gurruchaga, José Luis
author_role author
author2 Luque Montoro, Miriam
Llavero Bernal, Francisco
Zugaza Gurruchaga, José Luis
author2_role author
author
author
dc.subject.none.fl_str_mv amyloid β1–42 oligomers
OGT
O-GlcNAcylation
Galectin–1
Galectin–1Serine 8–O–GlcNAcylation
Gal–1S8A
microglia
migration
topic amyloid β1–42 oligomers
OGT
O-GlcNAcylation
Galectin–1
Galectin–1Serine 8–O–GlcNAcylation
Gal–1S8A
microglia
migration
description Protein O–GlcNAcylation has been associated with neurodegenerative diseases such as Alzheimer’s disease (AD). The O–GlcNAcylation of the Amyloid Precursor Protein (APP) regulates both the trafficking and the processing of the APP through the amyloidogenic pathway, resulting in the release and aggregation of the Aβ1–42 peptide. Microglia clears Aβ aggregates and dead cells to maintain brain homeostasis. Here, using LC-MS/MS, we revealed that the Aβ1–42 oligomers modify the microglia O-GlcNAcome. We identified 55 proteins, focusing our research on Galectin-1 protein since it is a very versatile protein from a functional point of view. Combining biochemical with genetic approaches, we demonstrated that Aβ1–42 oligomers specifically target Galectin–1S8 O–GlcNAcylation via OGT. In addition to this, the Gal–1–O–GlcNAcylated form, in turn, controls human microglia migration. Given the importance of microglia migration in the progression of AD, this study reports the relationship between the Aβ1–42 oligomers and Serine 8–O–GlcNAcylation of Galectin–1 to drive microglial migration.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/62085
url http://hdl.handle.net/10810/62085
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.mdpi.com/2073-4409/12/14/1876
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869420217406324736
score 15.300719

Registos relacionados