Gamma-secretase inhibitor Compound E restores normal BK-dependent ERK activation in PS-1 (M146L) AD fibroblasts.

<p>PS-1 (M146L) AD and normal control human skin fibroblasts were treated with Gamma secretase inhibitor Compound E (1 or 10 nM) or DMSO vehicle control for 24 hr and then stimulated with 250 nM BK for 0–30 min. Cell lysates were immunoblotted for ERK as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004655#pone-0004655-g006" target="_blank">Figure 6</a> and analyzed by Odyssey for ERK activation normalized to Tubulin as loading control. A representative blot is shown in (A). ERK activation was quantified as a percentage of basal activation in buffer-treated cells (0 min) pre-treated with DMSO or Compound E. ERK activity phenotypes are graphically represented in control fibroblasts compared with PS-1 (M146L) AD fibroblasts (B). All graphs show mean±S.E. Statistical analysis was performed via t-test with *p-value<0.05; n = 3.