Fig. 3: LRRK2 kinase inhibitors rescue PD-related pathophysiologic phenotypes in LRRK2 and GBA1 mutant neurons. Measurement of insoluble oxidized dopamine by near-IR fluorescence from LRRK2 G2019S.

a and R1441C c mutant DA neurons treated with 6166 or MLi-2. Treated cultures were also subjected to western blot analysis of phospho-S129 aSyn (P-S129), total aSyn, and tyrosine hydrolase (TH) with β-3-tubulin used as a loading control b, d. Measurement of relative levels of insoluble oxidized dopamine by near-IR fluorescence from DA neurons containing GBA1 E326K e or N370S h mutations. Treated cultures were also subjected to western blot analysis of P-S129, total aSyn, and TH with β-3-tubulin used as a loading control f, i. Representative images from additional DA neurons containing GBA1 E326K g or N370S j mutations treated with MLi-2 and stained with antibodies targeted to P-S129 and β-3-tubulin, scale bars, 50 µm. The data are presented as the mean ± SEM, n = 3; *p < 0.05, **p < 0.01 relative to untreated, one-way ANOVA followed by Tukey’s multiple comparison post hoc test. Source data are provided as a Source Data file.