Although one study showed that TDP-43 or mutant SOD1 overexpression resulted in neurodegeneration through hyperactive Notch1 signaling [41], most of studies cited here are consistent with our findings, suggesting that insufficient Notch1-Akt signaling may lead to neurotoxicity and motor neuron dysfunction in ALS. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.