Caspase signalling controls microglia activation and neurotoxicity.

Research output: Contribution to journalArticle

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.

Details

Authors
  • Miguel Burguillos Garcia
  • Tomas Deierborg
  • Edel Kavanagh
  • Annette Persson
  • Nabil Hajji
  • Albert Garcia-Quintanilla
  • Josefina Cano
  • Patrik Brundin
  • Elisabet Englund
  • Jose L Venero
  • Bertrand Joseph
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
  • Cancer and Oncology
Original languageEnglish
Pages (from-to)319-U214
JournalNature
Volume472
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

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)