An ICE inhibitor, z-VAD-DCB attenuates ischaemic brain damage in the rat

Inhibition of interleukin 1β converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage

“…Hence, deterioration of neurological function after acute injury may be reduced by administering cysteine protease inhibitors. Inhibition of ICE-like caspases attenuated ischemic cell death in rat cortex and striatum, as described in a preliminary report after permanent ischemia (44). Our findings were associated with behavioral improvement as well.…”

Cell death attenuation by `Usurpin', a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex

“…The caspases mediate apoptosis by cleaving a discrete subset of homeostatic, repair and structural proteins within dying cells which results in the cessation of normal cellular functions, the dismantling of the genome and structural constituents of the cell, and the packaging of cellular components into apoptotic corpses for engulfment by other cells Rosen and Casciola-Rosen, 1997). The central importance of caspases in these processes has been demonstrated with both macromolecular and peptide-based inhibitors, which prevent apoptosis from occurring in vitro and in vivo, as well as by genetic approaches (Bump et al, 1995;Devereaux et al, 1997;Hara et al, 1997;Kuida et al, 1996;Liston et al, 1996;Loddick et al, 1996;Nicholson et al, 1995;Xue and Horvitz, 1995;Zhou et al, 1997).…”

Anti-apoptotic oncogenes prevent caspase-dependent and independent commitment for cell death

“…Mice with a homozygous disruption of caspase 3 show a massive accumulation of developing neurons owing to an absence of programmed cell death in the brain (Kuida et al, 1996). Finally, inhibition of caspases by zVAD-DCB administration can limit the extent of neuronal cell death resulting from ischemia and reperfusion (Loddick et al, 1996) and inhibition of caspases with zVAD-fmk prevents cell death after CD95 ligation (Longthorne and Williams, 1997;Xiang et al, 1996). All of these studies argue that caspase activation can represent a cell's decision to live or die.…”