Fig. 4

The MEKi trametinib improves the motor function and extends the lifespan of the TDP-43 flies. A A schematic of the pharmacologic and behavioral tests of the MEKi trametinib. The expression of the UAS-hTDP-43 transgene (by elavGS) is induced on Day 1 of the adulthood of the flies with RU486. At the same time, trametinib at indicated concentrations is also added in the fly food. b-e Representative western blot image (b) and quantifications of phosphorylated dERK (p-dERK) normalized to total dERK (c) or to GAPDH (d) and hTDP-43 protein levels (e) in the brains of the elavGS > hTDP-43 flies. (f, g) qPCR analysis of the mRNA levels of the immune AMP genes AttC (f) and DptB (g) in the brain of the TDP-43 flies fed with indicated concentrations of trametinib. The mRNA levels are normalized to actin and shown as percentages to that of the control flies (elavGS > hTDP-43 + DMSO), which is set to 100%. h The climbing assays of the elavGS > hTDP-43 flies fed with indicated concentrations of trametinib. i The log-rank analysis of the survival curves indicates that trametinib extends the lifespan of the elavGS > hTDP-43 flies. Mean ± SEM; n = 3 in (c-g), n =  ~ 10 vials/group with ~ 20 flies each vial in (h), and the number (n) of flies tested in each group is as indicated in (i). One-way ANOVA; *p < 0.05, **p < 0.01, ***p < 0.001; ns, no significance