Knock-out of the neural death effector domain protein PEA-15 demonstrates that its expression protects astrocytes from TNF alpha-induced apoptosis

Apoptosis is a very general phenomenon, but only a few reports concern astr ocytes. Indeed, astrocytes express receptors for tumor necrosis factor (TNF ) alpha, a cytokine demonstrated on many cells and tissues to mediate apopt osis after recruitment of adaptor proteins containing a death effector doma in (DED). PEA-15 is a DED-containing protein prominently expressed in the C NS and particularly abundant in astrocytes. This led us to investigate if P EA-15 expression could be involved in astrocytic protection against deleter ious effects of TNF. In vitro assays evidence that PEA-15 may bind to DED-c ontaining protein FADD and caspase-8 known to be apical adaptors of the TNF apoptotic signaling. After generation of PEA-15 null mutant mice, our resu lts demonstrate that PEA-15 expression increases astrocyte survival after e xposure to TNF.