Figure 3
From: Huntingtin cleavage product A forms in neurons and is reduced by gamma-secretase inhibitors
Compound P1-N031 shows dose-dependent inhibition of cpA in X57 cells. (a) Example western blot of lysates from clonal striatal cells transfected with H287-18Q-HA and treated with small molecule P1-N031 (Novartis) or carrier (DMSO). Arrowhead identifies the intact htt1-287-HA and arrows show cpA and cpB. The compound P1-N031 inhibits in a dose-dependent manner levels of cpA, but not cpB. (b) Dose-response curves for cpA (solid line) and cpB (dashed line). Y-axis is densitometry of ratio of signal for protease fragment relative to intact Htt1-287 to average DMSO. X-axis is concentration of compound in μM. Error bars represent sd, * p < 0.05, Friedman's test with Dunn's multiple comparison post-test (N = 3 /dose).