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2-Chlorodeoxyadenosine (Cladribine) preferentially inhibits the biological activity of microglial cells

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dc.contributor.author Aybar, Florencia
dc.contributor.author Pérez, María Julia
dc.contributor.author Marcora, María Silvina
dc.contributor.author Samman, María Eugenia
dc.contributor.author Marrodán, Mariano
dc.contributor.author Pasquini, Juana María
dc.contributor.author Correale, Jorge
dc.date.accessioned 2023-12-21T12:34:59Z
dc.date.available 2023-12-21T12:34:59Z
dc.date.issued 2022-01-29
dc.identifier.citation Aybar F, Julia Perez M, Silvina Marcora M, Eugenia Samman M, Marrodan M, María Pasquini J, Correale J. 2-Chlorodeoxyadenosine (Cladribine) preferentially inhibits the biological activity of microglial cells. Int Immunopharmacol. 2022 Apr;105:108571. doi: 10.1016/j.intimp.2022.108571. Epub 2022 Jan 29. es_ES
dc.identifier.uri https://doi.org/10.1016/j.intimp.2022.108571
dc.identifier.uri https://repositorio.fleni.org.ar/xmlui/handle/123456789/929
dc.description.abstract Cladribine (2CdA) is a synthetic chlorinated purine nucleoside analogue which acts as a pro-drug requiring intracellular phosphorylation to be activated. It is biologically active in selected cell types, which results in a reduction of circulating T and B lymphocytes implicated in multiple sclerosis (MS) pathogenesis. In addition, 2CdA shows good central nervous system (CNS) penetration and can therefore exert its action on microglia and astrocytes. Therefore, we studied the effects of 2CdA on microglial cells and astrocytes, both emerging as potential targets for MS therapy. Other than its effects on the peripheral immune system, 2CdA induced the apoptosis of microglial cells, inhibited their proliferation and reduced the production of cytokines, particularly pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. These represent additional mechanisms of 2CdA that may contribute to limiting inflammatory pathways. By contrast, astrocytes showed resistance to the action of 2CdA, which may be explained by differences in its intracellular phosphorylation. Insights into the mechanism of action of and resistance to 2CdA in CNS-resident cells may prove crucial for its optimal use. es_ES
dc.language.iso eng es_ES
dc.publisher Elsevier Science es_ES
dc.subject Microglia es_ES
dc.subject Microglía es_ES
dc.subject Deoxycytidine Kinase es_ES
dc.subject Desoxicitidina Quinasa es_ES
dc.subject CladribinaEspañol es_ES
dc.subject Cladribine es_ES
dc.subject Astrocytes es_ES
dc.subject Astrocitos es_ES
dc.title 2-Chlorodeoxyadenosine (Cladribine) preferentially inhibits the biological activity of microglial cells es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.description.fil Fil: Marrodán, Mariano. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina.
dc.description.fil Fil: Correale, Jorge. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina.
dc.description.fil Fil: Aybar, Florencia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.description.fil Fil: Pérez, María Julia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.description.fil Fil: Marcora, María Silvina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.description.fil Fil: Samman, María Eugenia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.description.fil Fil: Pasquini, Juana María. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.relation.ispartofVOLUME 105
dc.relation.ispartofPAGINATION 108571
dc.relation.ispartofCOUNTRY Estados Unidos
dc.relation.ispartofCITY Nueva York
dc.relation.ispartofTITLE International immunopharmacology
dc.relation.ispartofISSN 1878-1705
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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