Multiple BACE1 inhibitors abnormally increase the BACE1 protein level in neurons by prolonging its half-life

Fig. 2

The elevated cellular level of BACE1 is specific to BACE1 inhibitor treatment. (A) Intracellular BACE1 were measured by ELISA after 24-h treatment of HEK-293-sw cells with pepstatin A (doses from 790 nM to 50 μM). All values are normalized to DMSO treatment (n = 3, means ± SD; some error bars too small to see). (B) Cellular BACE1 was measured by ELISA after 24-h treatment of HEK-293-sw cells with DAPT or else DAPT plus AZD3293 (doses from 78 nM to 10 μM). All values are normalized to DMSO treatment (n = 2, means ± SD; some error bars too small to see). (C) Cellular cathepsin B, TACE, and ADAM9 were measured by ELISA after 24-h treatment of HEK-293-sw cells with AZD3293 (doses from 0.6 nM to 10 μM) (n = 2, means ± SD; some error bars too small to see). Blue, orange, and red lines: cathepsin B, TACE, and ADAM9 levels with plain DMSO treatment, respectively. (D)…