Transcriptome-based screening in TARDBP/TDP-43 knock-in motor neurons identifies the NEDD8-activating enzyme inhibitor MLN4924.

Downregulation was confirmed in 1 out of 7 miRNAs selected for validation (has-miR-381-3p), although most miRNAs showed a clear trend toward decreased abundance relative to the isogenic control (Fig. 3 f).

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We observed a strong trend towards decreased levels of NEDD8-conjugated proteins upon treatment with MLN4924, though only reaching statistical significance in TDP-43 G348C MNs (Isog Ctrl P = 0.0799; TDP-43 A382T P = 0.0705; TDP-43 G348C P = 0.0266 by one-way ANOVA with Sidak’s multiple comparisons test) (Fig. 6 c, f, Supplementary Fig.

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