Most importantly, in this study, we are the first to report that increased SOCS3 levels (1) are directly associated with the increases in reactive astrocytes and microglia/macrophages in the ALS mice, and (2) are directly associated with the increases in the neuronal loss over the course of disease progression as early as at the pre-symptomatic stage and become more exaggerated in the early symptomatic stage. Here, SOCS3 is linked to amyotrophic lateral sclerosis.