Caspase-6 is postulated to be involved in neuronal degeneration and apoptosis [16, 17, 18, 20, 22, 30] , and detection of its activity in neuronal cultures is therefore of paramount interest. Previous studies have frequently used TUNEL assays as a measure of apoptosis, looked at VEIDase activity or the presence of the active caspase-6 fragment by Western blotting or immunostaining and assessed the presence of cleaved caspase-6 substrates [8, 18, 20, 21, 22] . The most specific methods to assess the effect of drug treatments on caspase-6 activity developed so far use antibodies against the active caspase-6 fragment, levels of which Figure 2 . VEID, but not lamin A+C, is cleaved in the absence of caspase-6. A: Caspase-6 protein (full-length, 32 kDa) is detected in MEFs generated from C6wt, but not C6ko mice. B: Endogenous lamin A protein (70 kDa) is cleaved in wt, but not C6ko MEFs after staurosporine stress for 4 h or longer. The antibody cross-reacts with full-length lamin C (60 kDa), and the cleaved band at 28 kDa has the same size for both lamin A+C (lower panel). C: MCF-7 cells express caspase-6, but not caspase-3 protein, whereas both C6wt and C6ko MEFs contain both caspases. hu: human, m: mouse, ns: non-specific band. D: MCF-7 cells were stressed with 5 mM camptothecin for different amounts of time and the cleavage of endogenous lamin A and C proteins was monitored by Western blotting with antibodies antibodies #2031 (full-length lamin A+C) and #2032 (C-terminal fragments). E: Schematic representation of lamin A and C and the caspase-6 cleavage site at AA 230. The N-terminal fragments generated by caspase-6 cleavage (red) have the same size (28 kDa) for both lamin A+C. F: C6wt or C6ko MEFs were stressed with 50 nM staurosporine for different amounts of time, lysates were generated and analyzed for cleavage of VEID-Afc. C6wt cells show a significant increase in fluorescence at each timepoint, the fluorescence signal obtained from C6ko lysates only reach a statistically significant difference from baseline after 4 h. would not necessarily change upon inhibitor treatment, or immunoprecipitation of active caspases with biotinylated zVADfmk, which depends on efficient precipitation and Western blotting for quantification [23] .