To investigate the potential involvement of HMGB1 in motor neuron-astrocyte communication, we evaluated the subcellular distribution of this protein in spinal motor neurons from non-transgenic mice (non-Tg) or transgenic mice over-expressing either the wild-type superoxide dismutase 1 (SOD1WT) or the ALS-linked mutant SOD1G93A protein at the most critical stages of disease progression, i.e., 30 days (asymptomatic stage), ∼100 days (onset of motor deficits) and ∼130 days of age (symptomatic stage). The gene discussed is HMGB1; the disease is amyotrophic lateral sclerosis.