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.