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Adenosine receptors as neuroinflammation modulators: role of A1 agonists and A2A antagonists

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dc.contributor.authorMartí Navia, Aleix
dc.contributor.authorDal Ben, Diego
dc.contributor.authorLambertucci, Catia
dc.contributor.authorSpinaci, Andrea
dc.contributor.authorVolpini, Rosaria
dc.contributor.authorMarques-Morgado, Inês
dc.contributor.authorCoelho, Joana E
dc.contributor.authorLopes, Luisa V.
dc.contributor.authorMarucci, Gabriella
dc.contributor.authorBuccioni, Michela
dc.date.accessioned2022-12-14T12:07:09Z
dc.date.available2022-12-14T12:07:09Z
dc.date.issued2020
dc.description© 2020 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 (http://creativecommons.org/licenses/by/4.0/).pt_PT
dc.description.abstractThe pathological condition of neuroinflammation is caused by the activation of the neuroimmune cells astrocytes and microglia. The autacoid adenosine seems to be an important neuromodulator in this condition. Its main receptors involved in the neuroinflammation modulation are A1AR and A2AAR. Evidence suggests that A1AR activation produces a neuroprotective effect and A2AARs block prevents neuroinflammation. The aim of this work is to elucidate the effects of these receptors in neuroinflammation using the partial agonist 2'-dCCPA (2-chloro-N6-cyclopentyl-2'-deoxyadenosine) (C1 KiA1AR = 550 nM, KiA2AAR = 24,800 nM, and KiA3AR = 5560 nM, α = 0.70, EC50A1AR = 832 nM) and the newly synthesized in house compound 8-chloro-9-ethyl-2-phenethoxyadenine (C2 KiA2AAR = 0.75 nM; KiA1AR = 17 nM and KiA3AR = 227 nM, IC50A2AAR = 251 nM unpublished results). The experiments were performed in in vitro and in in vivo models of neuroinflammation. Results showed that C1 was able to prevent the inflammatory effect induced by cytokine cocktail (TNF-α, IL-1β, and IFN-γ) while C2 possess both anti-inflammatory and antioxidant properties, counteracting both neuroinflammation in mixed glial cells and in an animal model of neuroinflammation. In conclusion, C2 is a potential candidate for neuroinflammation therapy.pt_PT
dc.description.sponsorshipThis research was funded by Cofinanziamento Assegno di Ricerca Volpini-Marucci, n° FPI400037 and by Fundação para a Ciência e a Tecnologia (PTDC/BIM-MEC/47778/2014). This work was supported by the University of Camerino (Fondo di ricerca di Ateneo) and by a grant from the Ministry of Research (PRIN N° 2015E8EMCM_008, 2015).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCells. 2020 Jul 21;9(7):1739pt_PT
dc.identifier.doi10.3390/cells9071739pt_PT
dc.identifier.eissn2073-4409
dc.identifier.urihttp://hdl.handle.net/10451/55387
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationPTDC/BIM-MEC/47778/2014pt_PT
dc.relation.publisherversionhttps://www.mdpi.com/journal/cellspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectA1AR agonistpt_PT
dc.subjectA2AAR antagonistpt_PT
dc.subjectLPSpt_PT
dc.subjectCytokinept_PT
dc.subjectGliapt_PT
dc.subjectNeuroinflammationpt_PT
dc.titleAdenosine receptors as neuroinflammation modulators: role of A1 agonists and A2A antagonistspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue7pt_PT
oaire.citation.titleCellspt_PT
oaire.citation.volume9pt_PT
person.familyNameMarques-Morgado
person.familyNameCoelho
person.familyNameLopes
person.givenNameInês
person.givenNameJoana
person.givenNameLuisa
person.identifier149432
person.identifier.ciencia-idC31D-A531-95EE
person.identifier.ciencia-idB310-839B-564D
person.identifier.ciencia-id4817-7194-C024
person.identifier.orcid0000-0003-3053-2772
person.identifier.orcid0000-0002-3964-6197
person.identifier.orcid0000-0001-8367-3005
person.identifier.scopus-author-id7101840699
person.identifier.scopus-author-id7102509159
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication98f0be71-f895-41a6-aa42-038d7902dd3e
relation.isAuthorOfPublication1301afd3-8056-4d54-983c-0bec935b2d75
relation.isAuthorOfPublicationdfc15976-b186-45d1-be1c-4592b336edb1
relation.isAuthorOfPublication.latestForDiscovery98f0be71-f895-41a6-aa42-038d7902dd3e

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