Fig. 6

Nilotinib (Nilo) treatment increases lifespan of TgA53T mice, decreases αS pathology, reduces accumulation of p53, and reduces autophagy deficits. a Cohorts of TgA53T mice were treated with either Nilo (n = 12) or DMSO (Vehicle) (n = 12) starting at 9 months of age. Mice were injected intraperitoneally three times weekly until disease onset progressing to end-stage. Nilo treatment significantly increases lifespan in the aged cohort and increased median survival from 378 days in the DMSO group to 437 in the Nilo treated group, *p < 0.05. b TgA53T mice were inoculated by IC/IS injection with 3000×g lysate from an end-stage TgA53T mice. Fourteen days following the inoculation, the mice were treated with either Nilo or DMSO (ip, 3X per week). Nilo significantly increased the lifespan in this cohort and increased median survival from 112 days post injection (dpi) for the DMSO treated group to 127 dpi for the Nilo group, **p < 0.01. c and d Total lysates (TL) of BST from Nilo or DMSO treated mice were immunoblotted for pY412c-Abl, c-Abl, pS15p53 and p53 (c) or pS129αS, αS, LC3 and p62 (d). The graph shows the quantitative analysis of the immunoblots. *p < 0.05; **p < 0.01; ***p < 0.001, Student’s t test. n = 3–6 different animal per group. There was a significant effect for treatment (p = 0.021) and interaction (p = 0.003) but not species (nTg or Tg, p = 0.119) for c-Abl activation by Two-way ANOVA analysis (c). A significant effect for treatment (p = 0.041) but not species (p = 0.143) or interaction (p = 0.134) was found for p53 activation by Two-way ANOVA (c). A significant effect for treatment (p = 0.025) and interaction (p = 0.003) for pS129αS level by Two-way ANOVA (d). A significant effect for treatment (p = 0.01) and interaction (p = 0.027) for p62 level by Two-way ANOVA (d)