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. Structured summary of protein interactions: SOD1 and SOD1 bind by biophysical (View interaction) SOD1 and SOD1 bind by cosedimentation in solution (View interaction) SOD1 and SOD1 bind by transmission electron microscopy (View interaction) (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.