S100B inhibition protects from chronic experimental autoimmune encephalomyelitis

Detalhes bibliográficos
Autor(a) principal: Barros, Catarina
Data de Publicação: 2022
Outros Autores: Barateiro, Andreia, Neto, Alexandre, Soromenho, Beatriz, Basto, Afonso, Mateus, Joana, Xapelli, Sara, Sebastião, Ana M, Brites, Dora, Graca, Luis, Fernandes, Adelaide
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/59501
Resumo: © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
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spelling S100B inhibition protects from chronic experimental autoimmune encephalomyelitisS100BExperimental autoimmune encephalomyelitisImmunityMultiple sclerosisNeuroinflammation© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Studies have correlated excessive S100B, a small inflammatory molecule, with demyelination and associated inflammatory processes occurring in multiple sclerosis. The relevance of S100B in multiple sclerosis pathology brought an emerging curiosity highlighting its use as a potential therapeutic target to reduce damage during the multiple sclerosis course, namely during inflammatory relapses. We examined the relevance of S100B and further investigated the potential of S100B-neutralizing small-molecule pentamidine in chronic experimental autoimmune encephalomyelitis. S100B depletion had beneficial pathological outcomes and based on promising results of a variety of S100B blockade strategies in an ex vivo demyelinating model, we choose pentamidine to assay its role in the in vivo experimental autoimmune encephalomyelitis. We report that pentamidine prevents more aggressive clinical symptoms and improves recovery of chronic experimental autoimmune encephalomyelitis. Blockade of S100B by pentamidine protects against oligodendrogenesis impairment and neuroinflammation by reducing astrocyte reactivity and microglia pro-inflammatory phenotype. Pentamidine also increased regulatory T cell density in the spinal cord suggesting an additional immunomodulatory action. These results showed the relevance of S100B as a main driver of neuroinflammation in experimental autoimmune encephalomyelitis and identified an uncharacterized mode of action of pentamidine, strengthening the possibility to use this drug as an anti-inflammatory and remyelinating therapy for progressive multiple sclerosis.This work was funded by grants from Ordem dos Farmacêuticos (AF), Merck KGaA (AF) and Fundação de Ciênciase Tecnologia (UIDB/04138/2020; UIDP/04138/2020) (iMed.ULisboa).Oxford University PressRepositório da Universidade de LisboaBarros, CatarinaBarateiro, AndreiaNeto, AlexandreSoromenho, BeatrizBasto, AfonsoMateus, JoanaXapelli, SaraSebastião, Ana MBrites, DoraGraca, LuisFernandes, Adelaide2023-09-28T15:55:17Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/59501engBrain Commun. 2022 Mar 25;4(3):fcac07610.1093/braincomms/fcac0762632-1297info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:08:42Zoai:repositorio.ul.pt:10451/59501Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:09:26.005894Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv S100B inhibition protects from chronic experimental autoimmune encephalomyelitis
title S100B inhibition protects from chronic experimental autoimmune encephalomyelitis
spellingShingle S100B inhibition protects from chronic experimental autoimmune encephalomyelitis
Barros, Catarina
S100B
Experimental autoimmune encephalomyelitis
Immunity
Multiple sclerosis
Neuroinflammation
title_short S100B inhibition protects from chronic experimental autoimmune encephalomyelitis
title_full S100B inhibition protects from chronic experimental autoimmune encephalomyelitis
title_fullStr S100B inhibition protects from chronic experimental autoimmune encephalomyelitis
title_full_unstemmed S100B inhibition protects from chronic experimental autoimmune encephalomyelitis
title_sort S100B inhibition protects from chronic experimental autoimmune encephalomyelitis
author Barros, Catarina
author_facet Barros, Catarina
Barateiro, Andreia
Neto, Alexandre
Soromenho, Beatriz
Basto, Afonso
Mateus, Joana
Xapelli, Sara
Sebastião, Ana M
Brites, Dora
Graca, Luis
Fernandes, Adelaide
author_role author
author2 Barateiro, Andreia
Neto, Alexandre
Soromenho, Beatriz
Basto, Afonso
Mateus, Joana
Xapelli, Sara
Sebastião, Ana M
Brites, Dora
Graca, Luis
Fernandes, Adelaide
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Barros, Catarina
Barateiro, Andreia
Neto, Alexandre
Soromenho, Beatriz
Basto, Afonso
Mateus, Joana
Xapelli, Sara
Sebastião, Ana M
Brites, Dora
Graca, Luis
Fernandes, Adelaide
dc.subject.por.fl_str_mv S100B
Experimental autoimmune encephalomyelitis
Immunity
Multiple sclerosis
Neuroinflammation
topic S100B
Experimental autoimmune encephalomyelitis
Immunity
Multiple sclerosis
Neuroinflammation
description © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-01-01T00:00:00Z
2023-09-28T15:55:17Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/59501
url http://hdl.handle.net/10451/59501
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Brain Commun. 2022 Mar 25;4(3):fcac076
10.1093/braincomms/fcac076
2632-1297
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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