dc.creator | Kavanagh, Edel T. | es |
dc.creator | Rodhe, Johanna | es |
dc.creator | Burguillos García, Miguel Ángel | es |
dc.creator | Venero Recio, José Luis | es |
dc.creator | Joseph, Bertrand | es |
dc.date.accessioned | 2016-05-24T12:37:38Z | |
dc.date.available | 2016-05-24T12:37:38Z | |
dc.date.issued | 2014 | |
dc.identifier.citation | Kavanagh, E.T., Rodhe, J., Burguillos García, M.Á., Venero Recio, J.L. y Joseph, B. (2014). Regulation of caspase-3 processing by cIAP2 controls the switch between pro-inflammatory activation and cell death in microglia. Cell death and disease, 5 (12), 1-9. | |
dc.identifier.issn | 2041-4889 | es |
dc.identifier.uri | http://hdl.handle.net/11441/41542 | |
dc.description.abstract | The activation of microglia, resident immune cells of the central nervous system, and inflammation-mediated neurotoxicity are
typical features of neurodegenerative diseases, for example, Alzheimer's and Parkinson's diseases. An unexpected role of
caspase-3, commonly known to have executioner role for apoptosis, was uncovered in the microglia activation process. A central
question emerging from this finding is what prevents caspase-3 during the microglia activation from killing those cells? Caspase-3
activation occurs as a two-step process, where the zymogen is first cleaved by upstream caspases, such as caspase-8, to form
intermediate, yet still active, p19/p12 complex; thereafter, autocatalytic processing generates the fully mature p17/p12 form of the
enzyme. Here, we show that the induction of cellular inhibitor of apoptosis protein 2 (cIAP2) expression upon microglia activation
prevents the conversion of caspase-3 p19 subunit to p17 subunit and is responsible for restraining caspase-3 in terms of activity
and subcellular localization.We demonstrate that counteracting the repressive effect of cIAP2 on caspase-3 activation, using small
interfering RNA targeting cIAP2 or a SMAC mimetic such as the BV6 compound, reduced the pro-inflammatory activation of
microglia cells and promoted their death. We propose that the different caspase-3 functions in microglia, and potentially other cell
types, reside in the active caspase-3 complexes formed. These results also could indicate cIAP2 as a possible therapeutic target to
modulate microglia pro-inflammatory activation and associated neurotoxicity observed in neurodegenerative disorders. | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Nature Publishing Group | es |
dc.relation.ispartof | Cell death and disease, 5 (12), 1-9. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | Regulation of caspase-3 processing by cIAP2 controls the switch between pro-inflammatory activation and cell death in microglia | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular | es |
dc.relation.publisherversion | 10.1038/cddis.2014.514 | es |
dc.identifier.doi | http://dx.doi.org/10.1038/cddis.2014.514 | es |
idus.format.extent | 9 p. | es |
dc.journaltitle | Cell death and disease | es |
dc.publication.volumen | 5 | es |
dc.publication.issue | 12 | es |
dc.publication.initialPage | 1 | es |
dc.publication.endPage | 9 | es |
dc.identifier.idus | https://idus.us.es/xmlui/handle/11441/41542 | |