Artículo
Deletion of caspase-8 in mouse myeloid cells blocks microglia pro-inflammatory activation and confers protection in MPTP neurodegeneration model
Autor/es | Kavanagh, Edel T.
Burguillos García, Miguel Ángel Carrillo Jiménez, Alejandro Oliva Martín, María José Santiago Pavón, Martiniano Rodhe, Johanna Joseph, Bertrand Venero Recio, José Luis |
Departamento | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular |
Fecha de publicación | 2015 |
Fecha de depósito | 2017-02-22 |
Publicado en |
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Resumen | Increasing evidence involves sustained pro-inflammatory microglia activation in the pathogenesis of different neurodegenerative diseases, particularly Parkinson's disease (PD). We recently uncovered a completely novel and ... Increasing evidence involves sustained pro-inflammatory microglia activation in the pathogenesis of different neurodegenerative diseases, particularly Parkinson's disease (PD). We recently uncovered a completely novel and unexpected role for caspase-8 and its downstream substrates caspase-3/7 in the control of microglia activation and associated neurotoxicity to dopaminergic cells. To demonstrate the genetic evidence, mice bearing a floxed allele of CASP8 were crossed onto a transgenic line expressing Cre under the control of Lysozyme 2 gene. Analysis of caspase-8 gene deletion in brain microglia demonstrated a high efficiency in activated but not in resident microglia. Mice were challenged with lipopolysaccharide, a potent inducer of microglia activation, or with MPTP, which promotes specific dopaminergic cell damage and consequent reactive microgliosis. In neither of these models, CASP8 deletion appeared to affect the overall number of microglia expressing the pan specific microglia marker, Iba1. In contrast, CD16/CD32 expression, a microglial pro-inflammatory marker, was found to be negatively affected upon CASP8 deletion. Expression of additional proinflammatory markers were also found to be reduced in response to lipopolysaccharide. Of importance, reduced pro-inflammatory microglia activation was accompanied by a significant protection of the nigro-striatal dopaminergic system in the MPTP mouse model of PD. |
Agencias financiadoras | Ministerio de Economía y Competitividad (MINECO). España Junta de Andalucía |
Identificador del proyecto | info:eu-repo/grantAgreement/MINECO/SAF2012-39029
P10-CTS-6494 |
Cita | Kavanagh, E., Burguillos García, M.Á., Carrillo Jiménez, A., Oliva Martín, M.J., Santiago Pavón, M., Rodhe, J.,...,Venero Recio, J.L. (2015). Deletion of caspase-8 in mouse myeloid cells blocks microglia pro-inflammatory activation and confers protection in MPTP neurodegeneration model. Aging, 7 (9), 673-689. |
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