reported that ISG15 positively correlated with the degree of neuronal damage in an animal model of ALS with no obvious signs of inflammation, a model of cerebral ischemia, a model of brain injury induced by cortical shocks, and a mouse model of chronic neuronal damage induced by the viral protein HIV gp120, with high and significantly elevated ISG15 levels in areas of neuronal damage (54). This evidence concerns the gene ITIH4 and amyotrophic lateral sclerosis.