Fig. 4
From: Mutations in LRRK2 impair NF-κB pathway in iPSC-derived neurons
Effect of endogenous LRRK2 silencing on NF-κB target genes. a-h qRT-PCR analyses of inflammatory genes 5 days after LRRK2 silencing. The effect of LRRK2 silencing was evident in the regulation of RNA levels of COX-2, A20, and TNFR1. For COX-2, the effect of LRRK2 silencing was significant (two-way ANOVA, ** P = 0.0021,), and post hoc analyses revealed a significant effect of shLRRK2 on RNA levels specifically in LRRK2G2019S neurons (** P < 0.01). For A20, in addition to the effect of knocking down the expression of LRRK2 (two-way ANOVA, P < 0.0001), the presence of the mutations had also a significant effect (two-way ANOVA, ** P = 0.008). Subsequently, there was an interaction between shLRRK2 and genotype (two-way ANOVA, ** P = 0.008). Indeed, post hoc analyses showed that there was an effect of LRRK2 silencing on A20 levels in LRRK2G2010 (*** P < 0.001) and LRRK2R1441G neurons (** P < 0.01). Finally, for TNFR1, the effect of LRRK2 silencing was significant in all groups (two-way ANOVA *** P < 0.0001; post hoc tests: *** P < 0.001 in Control WT and LRRK2G2019S and ** P < 0.01 in LRRK2R1441G). Mock cells were transduced with the empty vector. Lines represent the mean ± SEM of three to five independent silencing experiments