The executioners sing a new song: killer caspases activate microglia

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

Burguillos Garcia, MiguelLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)med-mub (författare)
Brundin, PatrikLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)mphy-pbr (författare)
Joseph, B.Karolinska Institutet (författare)
Burguillos, MAKarolinska Institutet (författare)
Institutionen för experimentell medicinsk vetenskapMedicinska fakulteten (creator_code:org_t)

Ingår i:Cell Death and Differentiation: Springer Science and Business Media LLC18:11, s. 1679-16911350-90471476-5403

Av författaren/redakt...: Venero, J. L.; Burguillos Garci ...; Brundin, Patrik; Joseph, B.; Burguillos, MA

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Neurovetenskaper

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