Artículo
Caspase signalling controls microglia activation and neurotoxicity
Autor/es | Burguillos García, Miguel Ángel
Deierborg, Tomas Kavanagh, Edel T. Persson, Annette Hajji, Nabil García Quintanilla, Alberto Cano, Josefina Brundin, Patrik Englund, Elisabet Venero Recio, José Luis Joseph, Bertrand |
Departamento | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular |
Fecha de publicación | 2011-04-11 |
Fecha de depósito | 2024-01-11 |
Publicado en |
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Resumen | Activation of microglia and inflammation-mediated neurotoxicity are suggested to play a decisive role in the pathogenesis of several neurodegenerative disorders. Activated microglia release pro-inflammatory factors that ... Activation of microglia and inflammation-mediated neurotoxicity are suggested to play a decisive role in the pathogenesis of several neurodegenerative disorders. Activated microglia release pro-inflammatory factors that may be neurotoxic. Here we show that the orderly activation of caspase-8 and caspase-3/7, known executioners of apoptotic cell death, regulate microglia activation through a protein kinase C (PKC)-δ-dependent pathway. We find that stimulation of microglia with various inflammogens activates caspase-8 and caspase-3/7 in microglia without triggering cell death in vitro and in vivo. Knockdown or chemical inhibition of each of these caspases hindered microglia activation and consequently reduced neurotoxicity. We observe that these caspases are activated in microglia in the ventral mesencephalon of Parkinson's disease (PD) and the frontal cortex of individuals with Alzheimer's disease (AD). Taken together, we show that caspase-8 and caspase-3/7 are involved in regulating microglia activation. We conclude that inhibition of these caspases could be neuroprotective by targeting the microglia rather than the neurons themselves. |
Agencias financiadoras | Ministerio de Ciencia y Tecnología (MCYT). España |
Identificador del proyecto | SAF2006-04119
2009-13778 |
Cita | Burguillos García, M.Á., Deierborg, T., Kavanagh, E.T., Persson, A., Hajji, N., García Quintanilla, A.,...,Joseph, B. (2011). Caspase signalling controls microglia activation and neurotoxicity. Nature, 472 (7343), 319-324. https://doi.org/10.1038/nature09788. |
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