Although the preceding studies suggest a role for caspases in neurotrophin
withdrawal-induced apoptosis, identifying the caspase(s) involved has proven
unexpectedly difficult. Because caspase-2 was originally identified as a mouse
brain embryonic transcript down-regulated in late stages of brain development,
172 there was considerable speculation that this caspase might play a
particularly important role in neuronal PCD resulting from neurotrophin deprivation.
Consistent with this possibility, transfection with caspase-2 cDNA
induce apoptosis in sympathetic neurons173 and neuroblastoma cells.174 Transfection
with a variety of caspase cDNAs, however, has been observed to induce
apoptosis in other cell systems, making it difficult to interpret this observation
(see Chapter 11 by Kaufmann et al.).