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[Preprint]. 2023 Mar 14:rs.3.rs-2617979. [Version 1] doi: 10.21203/rs.3.rs-2617979/v1

Figure 5. Dose-dependent reduction in Tau in human iPSC-neurons treated with cardiac glycosides.

Figure 5

WT and P301L neurons were differentiated for 6 weeks, then treated with cardiac glycosides for 24h or 72h. a, Representative western blot for WT neurons treated with proscillaridin A (ProsA). A dose-dependent reduction in total Tau and p-Tau S396 was observed at both 24h and 72h. b-c, In parallel, a reduction in MAPT mRNA and an increase in pre-miR-132 and miR-132 RNA were observed. d-f, Similar results were also observed in Tau P301L neurons by western blot (d) and mRNA (e, f) analysis. g-r, Western blot densitometry quantification of dose-dependent effects on Tau (TAU5), pTau S396, and the synaptic makers PSD95 and SYN1 in WT and P301L neurons treated for 24h or 72h. The yellow shades indicate compound concentrations leading to <30% loss of at least two synaptic/microtubule markers (N=1-2, error bars represent SEM, the dotted lines indicated that separate Western blots were put together).