Fig. 5

Terazosin rescues stress granule formation. (a) Images of TDP-43^WT and TDP-43^M337V mESC-MNs following NaArO₂-induced oxidative stress with treatment of increasing doses of terazosin. Red channel shows ChAT (motor neuron marker), green channel shows G3BP (stress granule marker), blue channel shows DAPI (nuclear marker). (b) TDP-43^M337V mESC-MNs show an impairment in the ability to produce stress granules compared to TDP-43^WT controls. Treatment with terazosin has no effect on stress granule formation in TDP-43^WT mESC-MNs (One-way ANOVA P = 0.013 with Dunnett's multiple comparisons: 0 µM Tz vs 0.625 µM Tz P = 0.95; 0 µM Tz vs 0.125 µM Tz P = 0.081; 0 µM Tz vs 2.5 µM P = 0.77), but increases the mean number of stress granules per motor neuron in TDP-43^M337V mESC-MNs in a dose-dependent manner (One-way ANOVA P < 0.0001 with Dunnett's multiple comparisons: 0 µM Tz vs 0.625 µM Tz P = 0.63; 0 µM Tz vs 0.125 µM Tz P = 0.015; 0 µM Tz vs 2.5 µM P < 0.0001). N = 3 differentiations, n > 30 random cells per differentiation. Error bars represent s.e.m., ns=non-significant, * = P < 0.05, *** = P < 0.001.