HMGB1 and amyotrophic lateral sclerosis: High motility group box 1 (HMGB1) is an ubiquitously expressed nuclear protein but also an extracellular mediator of RAGE and TLR4 activation, two proteins implicated in the neuroinflammatory pathways observed in ALS (Brites and Vaz, 2014; Lee et al., 2015).