SOD1 and amyotrophic lateral sclerosis: Based on these studies, it is plausible that wild-type neurons are targets of external NO or O•−2 that (1) accumulates in media conditioned by astrocytes carrying ALS mutants, or (2) is generated by surrounding wild-type glial cells (astrocytes and/or microglia) within the spinal cord culture via the action of factors present in the ACM (such as mutated or oxidized/misfolded SOD1 that is secreted by the ALS astrocytes).