The accumulation of DNA damage in motor neurons could be a possible cause of motor neuron apoptosis in ALS. p53 levels increase in vulnerable regions in individuals ALS (Fig. 11) (24,25). p53 accumulates in motor neurons in patients with ALS (Fig. 10A and C-E). This p53 is functionally active because it is phosphorylated (Fig. 10F). Neurons that accumulate DNA damage show activated p53 (Fig. 10E). The accumulation of DNA damage in motor neurons is thus a possible upstream pathogenic mechanism in ALS.