(A) Model of the mechanism by which SOD1-G93A microglia induce MN death in ALS. The NF-κB pathway is initiated in SOD1-G93A microglia by a SOD1-G93A-dependent mechanism leading to microglial activation and subsequently, MN death via inflammatory pathways. Inhibition of microglial NF-κB in ALS mice blocks microglial activation, down-regulates pro-inflammatory markers, and delays MN death.
(B) Model of IKKβCA mice in which NF-κB is constitutively active only in myeloid cells. Microglia in these mice exhibit a pro-inflammatory phenotype which induces MN death in a mutant SOD1-independent mechanism.