Fig. 8: Pharmacological inhibition of TDP-43 toxicity rescues nucleocytoplasmic transport function caused by TDP-43 pathology.
From: TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD
a, Overexpression of TDP-CTF or mutant TDP-43Q331K increases cell death in transfected cortical neurons compared to GFP. Treatment with 50 nM KPT-335 for 24 hrs reduced cell death in both TDP-CTF and TDP-43Q331K. b, Abnormal nuclear morphology with lamin B staining in neurons expressing TDP-CTF or TDP-43Q331K is rescued by treatment with 50 nM KPT-335. c, Locomotion defects in larvae expressing human TDP-43WT and TDP-43G298S are ameliorated by treatment with 1 μM but not 5 μM PT-335 or KPT-276. Graphs represent quartiles (boxes), 50th percentiles (center lines) and range (whiskers). Five independent experiments for a (circles represent each independent experiment; *P < 0.05, **P < 0.01, ***P < 0.001, two-way ANOVA), four independent experiments for b (circles represent each independent experiment; *P < 0.05, ***P < 0.001, two-way ANOVA) and c (circles represent n = 30 animals; **P < 0.01, ***P < 0.001, two-way ANOVA). Bonferroni’s post hoc test. Full statistical details are provided in Supplementary Table 4.
