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. Author manuscript; available in PMC: 2014 Mar 1.
Published in final edited form as: Biol Psychiatry. 2012 Nov 7;73(5):464–471. doi: 10.1016/j.biopsych.2012.08.027

Fig 4. Mechanism of anti-tau activity is D2 receptor antagonism.

Fig 4

A. Loss of DOP-2 and DOP-3 partially suppresses tauopathy phenotype. The motility of T337, T337;dop-2, T337;dop-3, and T337;dop-2;dop-3 young adult animals were compared in a liquid thrashing assay. T337;dop-2;dop-3 significantly improved (p<0.001) swimming compared to T337. Statistical analysis conducted was the Kruskal-Wallis test, followed by Dunns post-test. B. Loss of DOP-2 and DOP-3 suppresses neuron loss (p=0.0009) Statistical analysis was conducted using a Mann-Whitney, two-tailed test. C. Loss of both DOP-2 and DOP-3 reduces tau aggregation. Individual mixed populations of T337 (100% insol tau), T337;dop-2 (140% insol tau), T337;dop-3 (265% insol tau), and T337;dop-2;dop-3 (54% insol tau) worms were grown. Worms were subjected to a sequential extraction of tau using buffers of increasing solubilizing strength. Only T337;dop-2;dop-3 reduced the levels of detergent insoluble tau. D. Knockdown of D2 receptor reduces tau aggregation in HEK/tau cells. Equivalent pellets of HEK/tau cells with or without D2 receptor targeting RNAi were subjected to sequential extraction of tau using buffers of increasing solubilizing strength. Drd2 siRNA treatment reduced insoluble tau (normalized to soluble tau) relative to a scrambled siRNA control by 55%.