Cathepsin D (CathD) and B (CathB) inhibitors exacerbate 145QmHtt-induced cell death in cortical neurons. A. 145QmHtt transfected neurons exhibited increased cell death. Primary cortical neurons were transfected with 23QHtt and 145QmHtt constructs. At 9 DIV, neurons were immunostained by anti-Htt Ab2166 and nuclei were stained by Hoechst. Arrows point to the pyknotic nuclei. Scale bar = 10 micron. B. 3-MA, pepstatin A and E64d exacerbated 145QmHtt-induced neuron death. The combined use of pepA and E64d further exacerbated 145Q-mhtt-induced neuron death. Primary cortical neurons (9 DIV) were treated with 3-MA (10mM), CathD and B inhibitors, pepstatin A (15 μM) and E64d (30 μM), respectively, for 24 hr. Con = empty vector control. Neuronal cell death was scored by counting pyknotic nuclei after Hoescht staining. There is no statistic significant difference in 23QHtt transfected neurons in the absence or presence of any of the chemicals. *p < 0.05 Student t-test compared to no inhibitor. †p < 0.05 compared to 23Q transfection. **p < 0.05 Student t-test compared to either pepA or E64d alone.