Figure 2
From: ALS-linked FUS exerts a gain of toxic function involving aberrant p38 MAPK activation
The inhibitory effect of mutant-FUS on FAT is mediated by activated p38 MAPK. FUS R521G was co-perfused with the indicated pharmacological inhibitor or Hsp110 into squid axoplasm and fast axonal transport evaluated as described in Fig. 1. (A–C) Co-perfusion of the pharmacological JNK kinase inhibitor SP600125 (0.5 μM) with R521G failed to rescue FAT inhibition. In contrast, inhibition of the p38 MAPK pathway by co-perfusion of either SB203850 (5 μM) or NQDI-1 (20 μM) prevented the toxic effects of FUS R521G on FAT (A,B,D,E). (F) Similarly, co-perfusion of Hsp110 (0.6 μM) and R521G ameliorated the inhibition of FAT by mutant FUS. Those conditions with statistical significance (p < 0.05) relative to FUS R521G are denoted by *, determined by one-way Anova and Tukey post-hoc test for multiple comparisons.
