Figure 2.

ISRIB restores translation in prion-diseased mice, downstream of eIF2α phosphorylation. (a) ISRIB treatment (blue bars) lowers ATF4 levels while leaving eIF2α-P unchanged in prion-diseased mice when compared with vehicle treated (gray bars) animals, confirming its site of action downstream of eIF2α-P. Representative immunoblots of hippocampal lysates and bar chart quantitating relative levels of proteins in three independent samples are shown. (b) ISRIB treatment partially restores translation as measured by [³⁵S]-methionine incorporation into hippocampal slices, compared with vehicle-treated animals (n=3-4 for each group). ***P<0.001, Student's t-test, two-tailed. Bar graphs show mean values±S.E.M.