SHH and amyotrophic lateral sclerosis: Based on earlier observations showing the involvement of IFN-γ in the paradoxical dysregulation of Shh-Gli1 pathway in neural stem cells in a model of autoimmune encephalomyelitis [54], and that TNF-α and IFN-γ synergistically induce inflammation, oxidative damage, and motor neuron apoptosis in rat spinal cord embryonic explants [55], we hypothesized that the inhibitory effect observed in our Shh-LTII assay could be related to elevated IFN-γ and TNF-α, and/or other cytokines present in the CSF of ALS patients.