FIGURE 4.

NIH Clinical Collection (NCC) small molecules inhibit α‐synuclein oligomer‐induced trafficking deficits. Treatment of primary neurons with α‐synuclein oligomer (1.0 μM final concentration) caused significant deficits in membrane trafficking rates (red dot) when compared with vehicle alone (blue dot, p < 0.0001, One‐way ANOVA, Dunnett's multiple comparisons). Seven hundred and twenty‐five NIH small molecules were tested in single‐point screens (data not shown) for their ability to block oligomer‐induced deficits and a subset of hit compounds (a–f) were tested in a range of doses with select examples shown above. Addition of (a) bupropion, (b) irbesartan, or (c) carmofur weakly inhibited α‐synuclein oligomer‐induced trafficking deficits. (d) Lovastatin and (e) carbamazepine inhibited deficits at low concentrations but were toxic at concentrations >5 µM. (f) Thioridazine was cytotoxic at concentrations >1 µM. All data points represent means ± SD for four to six replicate experiments in separate cell culture preparations [Color figure can be viewed at wileyonlinelibrary.com]