Caspase signalling controls microglia activation and neurotoxicity.

Research output: Contribution to journalArticle

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Caspase signalling controls microglia activation and neurotoxicity. / Burguillos Garcia, Miguel; Deierborg, Tomas; Kavanagh, Edel; Persson, Annette; Hajji, Nabil; Garcia-Quintanilla, Albert; Cano, Josefina; Brundin, Patrik; Englund, Elisabet; Venero, Jose L; Joseph, Bertrand.

In: Nature, Vol. 472, 2011, p. 319-U214.

Research output: Contribution to journalArticle

Harvard

Burguillos Garcia, M, Deierborg, T, Kavanagh, E, Persson, A, Hajji, N, Garcia-Quintanilla, A, Cano, J, Brundin, P, Englund, E, Venero, JL & Joseph, B 2011, 'Caspase signalling controls microglia activation and neurotoxicity.', Nature, vol. 472, pp. 319-U214. https://doi.org/10.1038/nature09788

APA

Burguillos Garcia, M., Deierborg, T., Kavanagh, E., Persson, A., Hajji, N., Garcia-Quintanilla, A., ... Joseph, B. (2011). Caspase signalling controls microglia activation and neurotoxicity. Nature, 472, 319-U214. https://doi.org/10.1038/nature09788

CBE

Burguillos Garcia M, Deierborg T, Kavanagh E, Persson A, Hajji N, Garcia-Quintanilla A, Cano J, Brundin P, Englund E, Venero JL, Joseph B. 2011. Caspase signalling controls microglia activation and neurotoxicity. Nature. 472:319-U214. https://doi.org/10.1038/nature09788

MLA

Vancouver

Burguillos Garcia M, Deierborg T, Kavanagh E, Persson A, Hajji N, Garcia-Quintanilla A et al. Caspase signalling controls microglia activation and neurotoxicity. Nature. 2011;472:319-U214. https://doi.org/10.1038/nature09788

Author

Burguillos Garcia, Miguel ; Deierborg, Tomas ; Kavanagh, Edel ; Persson, Annette ; Hajji, Nabil ; Garcia-Quintanilla, Albert ; Cano, Josefina ; Brundin, Patrik ; Englund, Elisabet ; Venero, Jose L ; Joseph, Bertrand. / Caspase signalling controls microglia activation and neurotoxicity. In: Nature. 2011 ; Vol. 472. pp. 319-U214.

RIS

TY - JOUR

T1 - Caspase signalling controls microglia activation and neurotoxicity.

AU - Burguillos Garcia, Miguel

AU - Deierborg, Tomas

AU - Kavanagh, Edel

AU - Persson, Annette

AU - Hajji, Nabil

AU - Garcia-Quintanilla, Albert

AU - Cano, Josefina

AU - Brundin, Patrik

AU - Englund, Elisabet

AU - Venero, Jose L

AU - Joseph, Bertrand

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000), Neuronal Survival (013212041)

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.1038/nature09788

DO - 10.1038/nature09788

M3 - Article

VL - 472

SP - 319-U214

JO - Nature

T2 - Nature

JF - Nature

SN - 0028-0836

ER -