CHUK and amyotrophic lateral sclerosis: Activation of NF-κB is associated with the release of pro-inflammatory cytokines, such as TNF-α and IL-1β,57 which have been shown cause neurotoxicity in various contexts.58,59 It is indicative of an upregulation of an inflammatory response mediated by IKKα/β kinases,60 which are negatively regulated by autophagy.61,62 It is possible that the more pro-inflammatory signature, the increased BA4 grey matter glial NF-κB activation, and the tendency toward higher TDP-43 burden seen in C9-ALS-FTSD cases with NPS1 is related to lower levels of negative regulation via autophagy.