FIGURE 8.

Inhibition of cytosolic Hsp90 activity reduces α-syn membrane dissociation. Dissociation of α-syn from presynaptic membranes was assessed in the absence or presence of 50 μm radicicol (left panel) or 20 μm geldanamycin (right panel). Synaptosomal membranes from Tg WT α-syn mice or α-syn-deficient cytosol were separately incubated with or without Hsp90 inhibitors for 10 min at 37 °C and then incubated together for another 10 min at 37 °C. Upper panels show representative immunoblots measuring the dissociation of membrane α-syn, and the lack of dissociation of integral membrane vesicle marker synaptophysin, into cytosol from experiments where inhibitor was added either to both membrane and cytosol (Memb/Cyt), only membrane (Memb), or only cytosol (Cyt). Lower panels show quantification of α-syn dissociation. Bars represent mean ± S.E. from seven to eight independent experiments and normalized to untreated controls. *, p < 0.05, one-way ANOVA with Bonferroni post-test.