FIG. 11.

Proposed pathways of proteasomal stress-induced cell death. In neocortical neurons, proteasome inhibition induces three distinct cell death pathways. Increased levels of p53 and the p53 target gene puma partially mediate caspase-dependent cell death. In addition, in a small number of neurons, mitochondrion-independent activation of caspases may occur. Moreover, lysosomal degradation and cathepsin-mediated cell death constitute another distinct cell death pathway, which may substitute for puma deficiency following proteotoxic stress.