γ-Secretase modulator ‘Torrey Pines’ counter-balances Aftin-5 effects. A) GSM ‘Torrey Pines’ dose-dependent effect on extracellular Aβ38, Aβ40, and Aβ42 levels in N2a-AβPP695 cells. Cells were exposed to various concentrations of ‘Torrey Pines’ compound for 18 h. Extracellular Aβ levels were measured by an ELISA assay and are expressed as fold change over the level of control, vehicle-treated cells. B) GSM ‘Torrey Pines’ dose-dependently inhibits Aftin-5 upregulation of Aβ42 and down-regulation of Aβ38. Cells were exposed to various concentrations of ‘Torrey Pines’ compound and 1 h later to 100 μM Aftin-5. Incubation was carried out for 18 h. Extracellular Aβ levels were measured by an ELISA assay and are expressed as fold change over the level of control, Aftin-5 treated cells. Representative of three independent experiments, errors bars represent standard deviation of triplicate values.