Fig. 6. SM875 inhibits prion replication in L929 mouse fibroblasts.

L929 mouse fibroblasts were infected with the RML prion strain and then propagated for five sequential passages before exposure to SM875 (indicated concentrations), anti-prion compound Fe³⁺-TMPyP (TP, 10 μM) or vehicle (0.1% DMSO) for 48 h. PrP^Sc loads were then estimated by treating cell lysates with PK and analyzing PrP content by western blotting (i). Signals were detected by probing membrane blots with anti-PrP antibody (D18). Results show that SM875 inhibits prion replication in a dose-dependent fashion, with the maximal effect (obtained at 10 μM) comparable to that of TP; (ii) the graph shows the densitometric quantification of all PK-resistant PrP bands from independent replicates (n ≥ 4). Quantification was obtained by densitometric analysis of the western blots, normalizing each signal on the corresponding PK-untreated lane and expressed as the percentage of vehicle (Vhc)-treated controls (**p < 0.01, *** p < 0.005, by one-way ANOVA test).