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The executioners sing a new song: killer caspases activate microglia

Venero, J. L.; Burguillos Garcia, Miguel LU ; Brundin, Patrik LU and Joseph, B. (2011) In Cell Death and Differentiation 18(11). p.1679-1691
Abstract
Activation of microglia and inflammation-mediated neurotoxicity are suggested to have key roles in the pathogenesis of several neurodegenerative disorders. We recently published an article in Nature revealing an unexpected role for executioner caspases in the microglia activation process. We showed that caspases 8 and 3/7, commonly known to have executioner roles for apoptosis, can promote microglia activation in the absence of death. We found these caspases to be activated in microglia of PD and AD subjects. Inhibition of this signaling pathway hindered microglia activation and importantly reduced neurotoxicity in cell and animal models of disease. Here we review evidence suggesting that microglia can have a key role in the pathology of... (More)
Activation of microglia and inflammation-mediated neurotoxicity are suggested to have key roles in the pathogenesis of several neurodegenerative disorders. We recently published an article in Nature revealing an unexpected role for executioner caspases in the microglia activation process. We showed that caspases 8 and 3/7, commonly known to have executioner roles for apoptosis, can promote microglia activation in the absence of death. We found these caspases to be activated in microglia of PD and AD subjects. Inhibition of this signaling pathway hindered microglia activation and importantly reduced neurotoxicity in cell and animal models of disease. Here we review evidence suggesting that microglia can have a key role in the pathology of neurodegenerative disorders. We discuss possible underlying mechanisms regulating their activation and neurotoxic effect. We focus on the provocative hypothesis that caspase inhibition can be neuroprotective by targeting the microglia rather than the neurons themselves. Cell Death and Differentiation (2011) 18, 1679-1691; doi: 10.1038/cdd.2011.107; published online 12 August 2011 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
microglia, caspases, neurodegenerative disorders
in
Cell Death and Differentiation
volume
18
issue
11
pages
1679 - 1691
publisher
Nature Publishing Group
external identifiers
  • wos:000295929600001
  • scopus:81155161863
ISSN
1350-9047
DOI
10.1038/cdd.2011.107
language
English
LU publication?
yes
id
3030011a-f38c-469a-9beb-59990f6143b4 (old id 2212068)
date added to LUP
2011-12-01 08:35:34
date last changed
2017-11-19 03:07:47
@article{3030011a-f38c-469a-9beb-59990f6143b4,
  abstract     = {Activation of microglia and inflammation-mediated neurotoxicity are suggested to have key roles in the pathogenesis of several neurodegenerative disorders. We recently published an article in Nature revealing an unexpected role for executioner caspases in the microglia activation process. We showed that caspases 8 and 3/7, commonly known to have executioner roles for apoptosis, can promote microglia activation in the absence of death. We found these caspases to be activated in microglia of PD and AD subjects. Inhibition of this signaling pathway hindered microglia activation and importantly reduced neurotoxicity in cell and animal models of disease. Here we review evidence suggesting that microglia can have a key role in the pathology of neurodegenerative disorders. We discuss possible underlying mechanisms regulating their activation and neurotoxic effect. We focus on the provocative hypothesis that caspase inhibition can be neuroprotective by targeting the microglia rather than the neurons themselves. Cell Death and Differentiation (2011) 18, 1679-1691; doi: 10.1038/cdd.2011.107; published online 12 August 2011},
  author       = {Venero, J. L. and Burguillos Garcia, Miguel and Brundin, Patrik and Joseph, B.},
  issn         = {1350-9047},
  keyword      = {microglia,caspases,neurodegenerative disorders},
  language     = {eng},
  number       = {11},
  pages        = {1679--1691},
  publisher    = {Nature Publishing Group},
  series       = {Cell Death and Differentiation},
  title        = {The executioners sing a new song: killer caspases activate microglia},
  url          = {http://dx.doi.org/10.1038/cdd.2011.107},
  volume       = {18},
  year         = {2011},
}