First, ALS may spread contiguously or non-contiguously following a ‘domino-prion-like’ propagation between neighboring neurons in a cell autonomous or non-cell autonomous manner, mutant SOD1 and normal TDP-43 can undergo a seeded aggregation similar to prions(Münch et al., 2011), and initiate the disease cascade that may lead to synaptic dysfunction and cell death. The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.