SOD1 and amyotrophic lateral sclerosis: Interestingly, in ALS conditions two of the factors known to stimulate neurocan cleavage, namely EGF and TGFbeta (Asher et al., 2000) are affected: at later stages of ALS, the TGFbeta pathway is persistently upregulated, leading, e.g., to excessive activation of microglia (Galbiati et al., 2020), and inhibitors of the EGF receptor have proven to be beneficial in the SOD1 mouse model of ALS (Le Pichon et al., 2013).