dc.creator | Viceconte, Nikenza | es |
dc.creator | Burguillos García, Miguel Ángel | es |
dc.creator | Herrera Carmona, Antonio José | es |
dc.creator | Martínez de Pablos, Rocío | es |
dc.creator | Joseph, Bertrand | es |
dc.creator | Venero Recio, José Luis | es |
dc.date.accessioned | 2016-05-24T12:31:56Z | |
dc.date.available | 2016-05-24T12:31:56Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Viceconte, N., Burguillos García, M.Á., Herrera Carmona, A.J., Martínez de Pablos, R., Joseph, B. y Venero Recio, J.L. (2015). Neuromelanin activates proinflammatory microglia through a caspase-8-dependent mechanism. Journal of Neuroinflammation, 12 (1), 1-15. | |
dc.identifier.issn | 1742-2094 | es |
dc.identifier.uri | http://hdl.handle.net/11441/41536 | |
dc.description.abstract | Background
We have uncovered a caspase-dependent (caspase-8/caspase-3/7) signaling governing microglia activation and associated neurotoxicity. Importantly, a profuse non-nuclear activation of cleaved caspases 8 and 3 was found in reactive microglia in the ventral mesencephalon from subjects with Parkinson’s disease, thus supporting the existence of endogenous factors activating microglia through a caspase-dependent mechanism. One obvious candidate is neuromelanin, which is an efficient proinflammogen in vivo and in vitro and has been shown to have a role in the pathogenesis of Parkinson’s disease. Consequently, the goal of this study is to test whether synthetic neuromelanin activates microglia in a caspase-dependent manner.
Results
We found an in-vivo upregulation of CD16/32 (M1 marker) in Iba1-immunolabeled microglia in the ventral mesencephalon after neuromelanin injection. In vitro experiments using BV2 cells, a microglia-derived cell line, demonstrated that synthetic neuromelanin induced a significant chemotactic response to BV2 microglial cells, along with typical morphological features of microglia activation, increased oxidative stress and induction of pattern-recognition receptors including Toll-like receptor 2, NOD2, and CD14. Analysis of IETDase (caspase-8) and DEVDase (caspase-3/7) activities in BV2 cells demonstrated a modest but significant increase of both activities in response to neuromelanin treatment, in the absence of cell death.
Conclusions
Caspase-8 inhibition prevented typical features of microglia activation, including morphological changes, a high rate of oxidative stress and expression of key proinflammatory cytokines and iNOS | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | BioMed Central | es |
dc.relation.ispartof | Journal of Neuroinflammation, 12 (1), 1-15. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | caspase-3 | es |
dc.subject | caspase-8 | es |
dc.subject | cytokines | es |
dc.subject | microglia | es |
dc.subject | neuroinflammation | es |
dc.subject | Parkinson’s disease | es |
dc.title | Neuromelanin activates proinflammatory microglia through a caspase-8-dependent mechanism | 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 | 10.1186/s12974-014-0228-x | es |
dc.identifier.doi | http://dx.doi.org/10.1186/s12974-014-0228-x | es |
idus.format.extent | 15 p. | es |
dc.journaltitle | Journal of Neuroinflammation | es |
dc.publication.volumen | 12 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | 1 | es |
dc.publication.endPage | 15 | es |
dc.identifier.idus | https://idus.us.es/xmlui/handle/11441/41536 | |