Fig. 1: Presenilin confers resistance to ferroptosis in multiple cell types and is affected by familial Alzheimer’s disease causative mutations.
From: Selective ferroptosis vulnerability due to familial Alzheimer’s disease presenilin mutations
Cell viability analyses performed using the MTT assay to compare ferroptosis resistance in mouse embryonic fibroblasts (MEFs), primary human fibroblasts and HT22 mouse hippocampal neurons to RSL3 (a, c, e, g, i) or erastin (b, d, f, h, j) at the concentrations shown, following 24 h incubation. Note: In i and j, “control” refers to matched negative-control HT22 cells transfected with non-targeting sgRNA contemporaneously with the generation of the PS1 KO and PS dKO HT22 cells, while “control*” is the contemporaneous and matched HT22 control for the subsequently created PS2 KO HT22 cells. Hence, PS1 KO and PS dKO HT22 should be compared to “control”, while PS2 KO should be compared to “control*”. Abbreviations: wildtype (WT), presenilin 1 knockout (PS1 KO), presenilin 2 knockout (PS2 KO), presenilin double-knockout (PS dKO), wild-type human sequence presenilin 1 (wt hPS1), L166P familial Alzheimer’s disease mutant human sequence presenilin 1 (L166P hPS1), I213T familial Alzheimer’s disease mutant human sequence presenilin 1 (I213T hPS1), healthy control human fibroblast (HC), A246E familial Alzheimer’s disease mutant presenilin 1 human fibroblast (PS1A246E FAD), N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT, 10 μM, γ-secretase inhibitor). Data points represent mean percentage survival relative to respective controls ± SEM, N = 12–16 from 3 to 4 independent experiments.
