The role of caspases in excitotoxic PCD remains uncertain. On the one
hand, proteolytic cleavage of procaspase-3 to the active protease184,187 and
appearance of corresponding DEVD-AFC cleavage activity in cytosol187-189
has been demonstrated in several model systems. Du et al. have observed
that treatment with the caspase inhibitor DEVD-aldehyde but not the inhibitor
YVAD-aldehyde protects superior cervical ganglion neurons from
NMDA-induced PCD.184 Likewise, the more promiscuous caspase inhibitor
Z-VAD-fluoromethylketone has been reported to inhibit valinomycininduced
PCD in cultured cortical neurons.190 To the extent that these inhibitors
are specific for caspases, the preceding observations suggest that one
or more caspases might play a critical role in excitotoxic PCD. On the other
hand, the same inhibitors have no effect on PCD in cerebellar granule neurons
exposed to depolarizing potassium concentrations,188,191 although other
caspase inhibitors such as Z-asp-2,6-dichloroacyloxybenzylmethyl ketone do
inhibit apoptosis in this model system.189
The role of caspases in excitotoxic PCD remains uncertain. On the one
hand, proteolytic cleavage of procaspase-3 to the active protease184,187 and
appearance of corresponding DEVD-AFC cleavage activity in cytosol187-189
has been demonstrated in several model systems. Du et al. have observed
that treatment with the caspase inhibitor DEVD-aldehyde but not the inhibitor
YVAD-aldehyde protects superior cervical ganglion neurons from
NMDA-induced PCD.184 Likewise, the more promiscuous caspase inhibitor
Z-VAD-fluoromethylketone has been reported to inhibit valinomycininduced
PCD in cultured cortical neurons.190 To the extent that these inhibitors
are specific for caspases, the preceding observations suggest that one
or more caspases might play a critical role in excitotoxic PCD. On the other
hand, the same inhibitors have no effect on PCD in cerebellar granule neurons
exposed to depolarizing potassium concentrations,188,191 although other
caspase inhibitors such as Z-asp-2,6-dichloroacyloxybenzylmethyl ketone do
inhibit apoptosis in this model system.189
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