early gene product that is upregulated during trophic factor withdrawalinduced
neuronal PCD.211
Studies exploring the role of caspases in the pathogenesis of neurodegenerative
diseases have only recently begun. Although Goldberg et al. have
reported that huntingtin can be cleaved by caspase-3 under cell-free conditions,
212 the cleavage of this substrate in intact cells and the contribution of
this cleavage to the pathogenesis of Huntington’s disease remain to be demonstrated.
In contrast, the cloning of the familial AD genes PS1 and
PS2/STM2213-215 resulted in analyses that suggest the direct involvement of
caspase-mediated PCD pathways in the pathogenesis of AD. Vito et al., for
example, reported that a cDNA homologous to PS2/STM2 is capable of
rescuing T cell hybridoma cells from Fas- and T cell receptor ligation-induced
apoptosis.205