Fig. 2
From: LRRK2 kinase inhibition reverses G2019S mutation-dependent effects on tau pathology progression
MLi-2 reduces total and pS935 LRRK2 and induces enlargement of pneumocytes. a The pharmacokinetic profile of unbound MLi-2 was measured in the plasma of mice following in-diet dosing. *P < 0.05, two-way ANOVA followed by Dunnett’s multiple comparison test to compare doses. b Total LRRK2 and pS935 LRRK2 were reduced in the kidney following 3-month treatment with MLi-2. *P < 0.05, ***P < 0.001, ****P < 0.0001, two-way ANOVA followed by Dunnett’s multiple comparison test to compare doses. c Total LRRK2 and pS935 LRRK2 were reduced in the kidney following 6-month treatment with MLi-2. ***P < 0.001, ****P < 0.0001, two-way ANOVA followed by Dunnett’s multiple comparison test to compare doses. Values were normalized to the wild-type mice treated with 0 mg/kg MLi-2 across time points. d Following hematoxylin and eosin staining, the lungs from mice treated with 450 mg/kg MLi-2 appear to have enlarged type II pneumocytes. Scale bars, 100 µm (main images), 10 µm (insets). e Pneumocytes were more easily observed and quantified following staining with an antibody targeting prosurfactant protein C (proSP-C). Scale bars, 100 µm (main images), 10 µm (insets). f, g proSP-positive pneumocytes were detected and quantified using an automated algorithm. Size distributions of measured signal are plotted. Wild-type and LRRK2G2019S knock-in mice treated for 3 months did not show a significant shift of distribution to larger sizes. ns = not significant, linear mixed effect model. N = 40 + cells/mouse from 4 to 7 mice/group. h, i After 6 months of treatment, wild-type (h) and LRRK2G2019S mice (i) showed larger distribution of proSP-C-positive pneumocytes at both doses of MLi-2 compared to mice not exposed to MLi-2. *P < 0.05, ns = not significant, linear mixed effect model. N = 40 + cells/mouse from 6 to 8 mice/group