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S100B inhibition protects from chronic experimental autoimmune encephalomyelitis

2022Artigo científico Acesso aberto
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dc.contributor.authorBarros, Catarina
dc.contributor.authorBarateiro, Andreia
dc.contributor.authorNeto, Alexandre
dc.contributor.authorSoromenho, Beatriz
dc.contributor.authorBasto, Afonso
dc.contributor.authorMateus, Joana
dc.contributor.authorXapelli, Sara
dc.contributor.authorSebastião, Ana M
dc.contributor.authorBrites, Dora
dc.contributor.authorGraca, Luis
dc.contributor.authorFernandes, Adelaide
dc.date.accessioned2023-09-28T15:55:17Z
dc.date.available2023-09-28T15:55:17Z
dc.date.issued2022
dc.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.pt_PT
dc.description.abstractStudies 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.pt_PT
dc.description.sponsorshipThis 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).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBrain Commun. 2022 Mar 25;4(3):fcac076pt_PT
dc.identifier.doi10.1093/braincomms/fcac076pt_PT
dc.identifier.eissn2632-1297
dc.identifier.urihttp://hdl.handle.net/10451/59501
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherOxford University Presspt_PT
dc.relationResearch Institute for Medicines
dc.relationResearch Institute for Medicines
dc.relation.publisherversionhttps://academic.oup.com/braincommspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectS100Bpt_PT
dc.subjectExperimental autoimmune encephalomyelitispt_PT
dc.subjectImmunitypt_PT
dc.subjectMultiple sclerosispt_PT
dc.subjectNeuroinflammationpt_PT
dc.titleS100B inhibition protects from chronic experimental autoimmune encephalomyelitispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberUIDB/04138/2020
oaire.awardNumberUIDP/04138/2020
oaire.awardTitleResearch Institute for Medicines
oaire.awardTitleResearch Institute for Medicines
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04138%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04138%2F2020/PT
oaire.citation.issue3pt_PT
oaire.citation.titleBrain Communicationspt_PT
oaire.citation.volume4pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNamePereira Barateiro Macedo
person.familyNameBasto
person.familyNameMateus
person.familyNameXapelli
person.familyNameSebastião
person.familyNameBrites
person.familyNameSilva Graca
person.familyNameFernandes
person.givenNameAndreia
person.givenNameAfonso
person.givenNameJoana
person.givenNameSara
person.givenNameAna M
person.givenNameDora
person.givenNameLuis Ricardo
person.givenNameAdelaide
person.identifierI-5746-2014
person.identifier694430
person.identifier129383
person.identifierM-8293-2013
person.identifierB-8887-2008
person.identifier.ciencia-idF01C-E625-FA82
person.identifier.ciencia-idA81A-BBD8-EB94
person.identifier.ciencia-id7F15-04AB-4818
person.identifier.ciencia-id7110-C8C3-ED42
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.ciencia-id921C-9B98-2867
person.identifier.ciencia-id6C19-B162-F561
person.identifier.ciencia-id2F17-4BE1-A074
person.identifier.orcid0000-0002-0378-4854
person.identifier.orcid0000-0002-4651-1338
person.identifier.orcid0000-0003-1606-292X
person.identifier.orcid0000-0001-6854-2509
person.identifier.orcid0000-0001-9030-6115
person.identifier.orcid0000-0002-3024-9777
person.identifier.orcid0000-0001-6935-8500
person.identifier.orcid0000-0002-2782-9519
person.identifier.scopus-author-id22940127500
person.identifier.scopus-author-id12785139100
person.identifier.scopus-author-id8721560200
person.identifier.scopus-author-id7004409879
person.identifier.scopus-author-id7004026610
person.identifier.scopus-author-id36138488700
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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