SOD1 and amyotrophic lateral sclerosis: Furthermore, intracellular inclusions containing ubiquitin and ubiquitin ligases were detected in familial ALS mutant mice, suggesting that mutant SOD1 is resistant to the UPS.177 Additionally, overexpressing mutant SOD1G93A in mice stimulates the formation of SOD1 aggregates and inhibits proteasome activity; the formation of SOD1 aggregates is reversible with the restoration of proteasome function.178 Moreover, it has been shown that reduced proteasomal activity can promote the accumulation of ALS protein aggregates177.