Figure 1
From: A novel specific PERK activator reduces toxicity and extends survival in Huntington's disease models
MK-28 rescues cells from ER stress-induced apoptosis. (A) General structural formula of the evaluated compounds. (B) Structures of A4 (Chembridge database) and novel derivatives. (C) Apoptosis rescue experiment using the murine striatal cell line expressing full-length polyQ-expanded Htt (STHdhQ111/111) incubated with the ER stress-inducer tunicamycin, shows that MK-28 and to a lesser extent A4 and MPGL1 are able to rescue the cells from apoptosis. Apoptosis was measured after 48 h of Tun exposure and PERK modulators were tested at different concentrations (0–100 μM). Results are expressed as average relative apoptosis rate ± SD of 3 independent experiments; apoptosis in the presence of tunicamycin and in the absence of other compounds was normalized to 100 to allow comparison between experiments. P values MK-28 vs. only Tun: 5 μM = 6 × 10–5, 50 μM = 1 × 10–9, 100 μM = 5 × 10–13; A4 vs. only Tun: 50 μM = 8 × 10–5, 100 μM = 0.001. (D) Rescue of STHdhQ111/111 cells compared to STHdhQ7/7 cells by MK-28. The graph shows average relative apoptosis rate ± SD of 3 independent experiments. P values vs. only Tun: STHdhQ7/7 cells: 5 μM = 2 × 10–5, 10 μM = 0.0002, 50 μM = 0.004, STHdh111/111 cells: 5 μM = 0.006, 10 μM = 0.008, 50 μM = 8 × 10–6.
