Figure 6.

Rapamycin Rescues P525L FUS-eGFP SG Pathology in SL iPSC-Derived Neurons

(A) Fluorescence confocal micrographs of P525L FUS-eGFP iPSC-derived neurons treated with 15 μM rapamycin in the presence of arsenite stress. Scale bar, 10 μm. Individual FUS-eGFP objects were identified and quantified. n = 3.

(B) Neurons with P525L FUS-eGFP have significantly more SGs per cell compared with WT and rapamycin reduces overall numbers.

(C) Neurons with P525L FUS-eGFP have significantly brighter SGs compared with WT. Rapamycin significantly decreases the brightness of WT and P525L FUS-eGFP SGs.

(D and E) P525L FUS-eGFP SGs in iPSC-derived neurons are significantly smaller compared with WT (D). However, total area of FUS-eGFP SGs per cell is significantly increased in neurons with P525L (E).

(F) Comparison of torkinib and rapamycin effect on neuronal SG area. Torkinib (top) significantly reduces SG area in both WT (left) and P525L (right) FUS-eGFP neurons after 5 hr of treatment. Rapamycin (bottom) is effective at the tested concentration only upon 24 hr treatment in P525L neurons (right). Effects on SG area appear earlier in WT cells (left), but are not as strong as under torkinib treatment.

Error bars indicate SEM. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001, and ^∗∗∗∗p < 0.0001.