Fig. 2.

PERK inhibitor treatment reduces eIF2α-P and ATF4 protein levels and restores protein synthesis rates in mutant tau-expressing rTg4510 mice. a tau⁺_P301L mice were treated twice daily by oral gavage from 6 months with either the PERK inhibitor, GSK2606414 50 mg/kg, (blue bars) or vehicle (grey bars) and tested at 8 months of age. b Immunostaining showed a significant reduction in PERK-P (red) and pSer²⁰²/Thr²⁰⁵-tau (AT8, green) staining in the hippocampus after GSK2606414 treatment. Graphs show quantification of relative intensity for PERK-P and ptau compared to transgene-negative mice (n = 3–5 mice, scale bar 20 μm). c PERK inhibitor treatment markedly reduced PERK-P, eIF2α-P and ATF4 protein levels in 8-month-old tau⁺_P301L mice, preventing the decline of global protein synthesis rates as determined by ³⁵S-methionine incorporation into protein (d) in comparison to vehicle-treated animals (n = 3 mice). Representative immunoblots of hippocampal lysates and bar charts quantitating protein levels (in three independent samples). All bar charts show mean ± SEM, *p < 0.05, **p < 0.01, using Student’s t test.