Because HMGB1 is normally located in the nucleus and translocates to the cytoplasm and extracellular space after traumatic events (Maroso et al., 2010; Choy et al., 2014; Sun et al., 2014; Agalave and Svensson, 2015), our data suggest that HMGB1 may be eventually released from stressed/damaged motor neurons into the extracellular milieu during ALS progression. This evidence concerns the gene HMGB1 and amyotrophic lateral sclerosis.