FIGURE 6.

Efficacy of TPZ compounds 10 and 11 in vitro. A, the indicated concentration of compound was applied to primary macrophages for 72 h and stimulated with LPS (100 ng/ml) for 6 h, and then lysates were evaluated by Western blot analysis for Ser(P)-935-LRRK2 and total LRRK2 levels. B, supernatants from LPS-exposed macrophages also treated with the indicated dose of compound 11 were evaluated for TNF release. Macrophages were derived from WT mice and G2019S-BAC mice (B) or knockout LRRK2 mice (C). Compound 11 demonstrated efficacy (*, p < 0.05) in reducing TNF release at a 2.5 μm dose in G2019S-LRRK2 macrophages but not in knockout LRRK2 macrophages. D, representative images of epifluorescence emitted by transfected primary hippocampal neurons at 10 days in vitro. Compound 11 was applied to the cultures, as indicated, for a 72-h period of time prior to image acquisition. E, neurite lengths were calculated from >100 neurons/condition and expressed as a percentage of the control (DMSO) average. *, p < 0.05, given by one-way analysis of variance with Tukey's post hoc corrections, and error bars represent mean ± S.E.