Fig. 4

Saracatinib blocks Aβ₄₂ oligomers toxic effects on hiPSC-derived cortical neurons. (A–D) Patch clamp electrophysiology recordings from the hiPSC-derived cortical neurons showed the blocking of the Aβ₄₂-induced defects by co-treatment with Saracatinib (10 nM) for 24 h, as demonstrated for the readouts of sodium currents (A), AP amplitude (B), spontaneous firing rate (C) and amplitude (D). (E) Analysis of cell function on cortical MEA LTP systems. A stimulus-induced increase in cell activity (i.e., firing frequency) was maintained in control samples dosed with Aβ_scr (5 µM), but was completely abolished within 1 h of Aβ₄₂ oligomer dosing. However, this Aβ₄₂-induced abolishment was blocked by co-treatment with Saracatinib (10 nM). Statistical analysis was performed via one-way ANOVA followed by Fisher’s LSD (α = 0.05) (N ≥ 25), *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001.