Our group previously identified several small molecules, including Methylene Blue, salubrinal and guanabenz, that target the ER stress response and were shown to have beneficial effects against mutant TDP-43 neuronal toxicity in models for ALS (Vaccaro et al., 2012a, 2013) and to have protective effects in models for hereditary spastic paraplegia (Julien et al., 2016). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.