Fig. 3

Assessment of MLi-2 in-diet dosing and LRRK2 inhibition. G2019S LRRK2 knock-in mice were fed chow containing different concentrations of MLi-2 to reach 10, 30, or 60 mg/kg/day dosing compared to G2019S knock-in and WT LRRK2 cohorts that were fed control chow. After 10-days, animals were sacrificed 2–3 h post start of their light cycle. Western blots of brain, kidney and lung tissue samples are shown. a, b Across all tissues, a significant increase in S1292 phosphorylation is seen in G2019S mice compared to WT animals which is ameliorated with increasing MLi-2 doses reaching WT levels at 60 mg/kg/day. c A dose-response was seen in S935 dephosphorylation that plateaued at 30 mg/kg/day. Quantitation of phosphorylation levels is calculated as S1292 and S935 levels over total LRRK2 (b and c: one-way ANOVA with Tukey’s post hoc, ****P < 0.0001, ***P < 0.0002, **P < 0.0021, *P < 0.0332; n = 3; SD bars shown; b F (14, 30) = 52.27, c F (14, 30) = 56.58)