Intracellular seeded aggregation of mutant Cu,Zn‐superoxide dismutase associated with amyotrophic lateral sclerosis

Once a protein adopts the fibrillar aggregate conformation, a seeding reaction becomes operative in which pre‐formed fibrils function as seeds for soluble protein molecules to be fibrillized. Such a seeding reaction accelerates the protein fibrillation in vitro; however, more investigation is required to test the seeded fibrillation inside cells. Here, we show that in vitro Cu,Zn‐superoxide dismutase (SOD1) fibrils are transduced into cells and function as seeds to trigger the aggregation of endogenously expressed SOD1. Seeded aggregation of mutant SOD1 will thus play roles in a molecular pathomechanism of SOD1‐linked amyotrophic lateral sclerosis.