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. 2021 Mar 31;7(14):eabb0799. doi: 10.1126/sciadv.abb0799

Fig. 5. APT1 inhibition via ML348 rescues behavioral symptoms, brain palmitoylation, and neuropathology in HD mice.

Fig. 5

(A) Pharmacokinetic analysis of brains (N = 3). (B) ABE assay for palmitoylated proteins. (C to E) Motor coordination and nonmotor behavior in HD mice. (C) Mean error score and time to cross the ladder from three trials (error score: H3 = 17.07, P = 0.0007, *P < 0.01; time: F3,50 = 4.478, *P < 0.05). (D) Mean number of falls from the fixed rotarod (F3,50 = 2.020, ***P < 0.001) and mean speed reached from the accelerating one (F3,50 = 0.4539, *P < 0.05). (E) Latency to eat in a 10-min test (F3,49 = 0.7710, *P < 0.05). (F) Immunoprecipitation of palmitoylated proteins in CAG140 treated mice (upper blot). Quantification of palmitoylated proteins relative to input (lower blot). (G) Airyscan confocal images of PSD95 (green), VGLUT1 (magenta), and Hoechst (blue) (scale bars, 5 μm). (H) Quantification of PSD95/VGLUT1 adjacent dots (F3,140 = 3.65, *P < 0.05). (I) Mutant HTT nuclear accumulation in CAG140-treated mice. EM48 immunostaining of striata from WT and CAG140 mice after ML348 or DMSO injection (scale bars, 50 μm). (J) Quantification of EM48-positive cells (t test, **P < 0.01). Error bars indicate SEM.