Unlike the acute injection of pathogenic SOD1 in this study where we observed the presence of pre-autophagosome and pre-lysosome formation within the time frame of both electrophysiological recordings and morphologic studies, ALS-associated mutant SOD1 in patients misfolds and accumulates gradually to pathologic levels over time, allowing adaptive changes in cellular and molecular mechanisms underlying synaptic transmission. Here, SOD1 is linked to amyotrophic lateral sclerosis.