Caspase signalling controls microglia activation and neurotoxicity.
Burguillos Garcia, Miguel LU ; Deierborg, Tomas LU ; Kavanagh, Edel ; Persson, Annette LU ; Hajji, Nabil ; Garcia-Quintanilla, Albert ; Cano, Josefina ; Brundin, Patrik LU ; Englund, Elisabet LU
and Venero, Jose L
, et al.
(2011)
In Nature
472.
p.214-319
- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1884133
- author
- Burguillos Garcia, Miguel
LU
; Deierborg, Tomas
LU
; Kavanagh, Edel
; Persson, Annette
LU
; Hajji, Nabil
; Garcia-Quintanilla, Albert
; Cano, Josefina
; Brundin, Patrik
LU
; Englund, Elisabet
LU
and Venero, Jose L
, et al. (More)
- Burguillos Garcia, Miguel
LU
; Deierborg, Tomas
LU
; Kavanagh, Edel
; Persson, Annette
LU
; Hajji, Nabil
; Garcia-Quintanilla, Albert
; Cano, Josefina
; Brundin, Patrik
LU
; Englund, Elisabet
LU
; Venero, Jose L
and Joseph, Bertrand
(Less)
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature
- volume
- 472
- pages
- 214 - 319
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000289724600033
- pmid:21389984
- scopus:79955485064
- pmid:21389984
- ISSN
- 0028-0836
- DOI
- 10.1038/nature09788
- language
- English
- LU publication?
- yes
- additional info
- 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)
- id
- d043360b-c18e-48bd-808a-5cf577cc898d (old id 1884133)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21389984?dopt=Abstract
- date added to LUP
- 2016-04-04 07:02:45
- date last changed
- 2022-05-16 19:20:46
@article{d043360b-c18e-48bd-808a-5cf577cc898d,
abstract = {{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.}},
author = {{Burguillos Garcia, Miguel and Deierborg, Tomas and Kavanagh, Edel and Persson, Annette and Hajji, Nabil and Garcia-Quintanilla, Albert and Cano, Josefina and Brundin, Patrik and Englund, Elisabet and Venero, Jose L and Joseph, Bertrand}},
issn = {{0028-0836}},
language = {{eng}},
pages = {{214--319}},
publisher = {{Nature Publishing Group}},
series = {{Nature}},
title = {{Caspase signalling controls microglia activation and neurotoxicity.}},
url = {{http://dx.doi.org/10.1038/nature09788}},
doi = {{10.1038/nature09788}},
volume = {{472}},
year = {{2011}},
}