Fig. 3
MEK/ERK-mediated immune overactivation contributes to TDP-43 pathogenesis. a A schematic of the MEK/ERK signaling and the IMD immune pathway. b-e qPCR analysis of the relative mRNA levels of the immune AMPs AttC and DptB in fly heads of the indicated genotypes (also see Table S1). f-g Adult-onset neuronal KD of AttC (f) or DptB (g) suppresses TDP-43-induced, age-dependent climbing decline. h-j Neuronal KD of Dnr1 significantly increases immune AMP expression (h), causes age-dependent motor deficits (i), and abolishes the suppressive effect of RNAi-Dsor1 on TDP-43-induced climbing defects (j). All mRNA levels are normalized to actin and shown as fold change (b, c, h) or percentage (d-e) to that of the corresponding control flies (which is set to 1 or 100%): UAS-lacZ in (b-c), RNAi-Luc in (d), RNAi-mCherry in (e), and RNAi- CtrlV.60200 flies in (h) (also see Methods and Table S1). Mean ± SEM; n = 3 in (b-e, h), and n =  ~ 10 vials/group with ~ 20 flies each vial in (f, g, I, j). Student’s t-test in (b-f, h, i) and one-way ANOVA in (g, j). *p < 0.05, **p < 0.01, ***p < 0.001