Vector-mediated knockdown of SNCA protects MPTP-treated mice against the onset of Parkinsonism. Mice (n = 8) treated with the vector/siRNA complexes were subjected to an acute dose of MPTP and subjected to fixed and accelerated speed rotarod behavioral assay 5 days later. Mice injected with saline were used as control, and the latency to fall off the rotarod was recorded in each case. Data are represented as means ± SEM. (a) Fixed speed rotarod: P = 0.0037 (**) by one-way ANOVA for multiple comparison. **P < 0.01, *P < 0.05 by Newman–Kauls posthoc analysis to test individual groups against MPTP-treated group. (b) Accelerated rotarod: P = 0.0183 (*) by one-way ANOVA for multiple comparison. *P < 0.05 by Newman–Kauls posthoc analysis to test individual groups against MPTP-treated group. (c) Dopaminergic neurodegeneration was assessed by tyrosine hydroxylase staining of the Substantia Nigra pars compacta. Data are represented as mean values ± SEM. P < 0.0001 (***) by one-way ANOVA for multiple comparison. ***P < 0.001 by Newman–Kauls posthoc analysis to test individual groups against MPTP-treated group. (d) Dopaminergic axonal loss was quantified by measuring striatal TH-immunoreactivity. Data are represented as mean values ± SEM. P = 0.0005 (***) by one-way ANOVA for multiple comparison. ***P < 0.001, **P < 0.01 by Newman–Kauls posthoc analysis to test individual groups against MPTP-treated group. c,d, Bar = 500 μm.