Endothelin-1 is richly expressed by reactive astrocytes in the spinal cord of the SOD1G93A mouse model of ALS and in sALS patients, and it has a toxic effect on cultured motor neurons via mechanisms mediated by reactive astrocytes, nitric oxide, and the PI3K/Akt pathway [61,62]. Here, AKT1 is linked to amyotrophic lateral sclerosis.