Fig. 3: LRP8 mediates resilience against ferroptosis.

Densitometric quantification and representative Western immunoblots of whole cell lysates probed with specific antibodies against LRP8 or loading control β-actin^ are shown for; wildtype (WT) and presenilin double-knockout (PS dKO) MEFs (a); healthy control (HC), sporadic Alzheimer’s disease (sAD) and FAD presenilin 1 mutant (PS1A246E FAD) human iPSC-derived basal cholinergic neurons (b); isogenic control (IC) and FAD presenilin 1 mutant (PS1ΔE9 FAD) human iPSC-derived basal cholinergic neurons (c) ^Note: Fig. 2b/3b and 2c/3c share the same β-actin blots as the displayed blots derive from the same original membranes that were successively probed with Lrp8, Gpx4 and β-actin antibodies (see “Supplemental Material – Original Blots”). Lrp8 mRNA in WT and PS dKO MEFs as measured by RT-qPCR (d). MTT cell viability assay of LRP8 KO and control MEFs following 24 h exposure to a discriminating dose range of RSL3 (e) or erastin (f). Western immunoblot and quantification of LRP8 and GPX4 in WT and PS dKO MEFs that have been transiently transfected with human sequence LRP8 or Vector cDNA (g). MTT cell viability assay of WT and PS dKO MEFs that have been transiently transfected with human sequence LRP8 or Vector cDNA after 24 h exposure to a dose range of RSL3 (h) or erastin (i). Densitometric analyses of proteins relative to β-actin are shown as mean values (±SEM) and individual points represent independent wells of cultured cells except in the iPSC neurons which are pooled from three wells. For the cell viability assay, data are mean values (±SEM), N = 12.