Preclinical data indicate that pharmacological or genetic activation of Nrf2, whether by electrophilic compounds such as dimethyl fumarate and nitro-fatty acids, dietary phytochemicals, like sulforaphane, or emerging targeted activators, can attenuate oxidative and proteotoxic stress, preserve mitochondrial integrity, modulate glial reactivity, and potentially restore RNA homeostasis in ALS models [34,35,36]. This evidence concerns the gene NFE2L2 and amyotrophic lateral sclerosis.