Intracellular seeded aggregation of mutant Cu, Zn‐superoxide dismutase associated with amyotrophic lateral sclerosis. Issue 16 (4th July 2013)

• Record Type: Journal Article
• Authors: Furukawa, Yoshiaki; Kaneko, Kumi; Watanabe, Shoji; Yamanaka, Koji; Nukina, Nobuyuki
• Is Part Of: FEBS letters. Volume 587:Issue 16(2013)
• Page Start: 2500
• Page End: 2505
• Publication Date: 2013-07-04
• Subjects: SOD1 -- ALS -- Protein aggregation -- Neurodegenerative disease -- Amyloid; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.06.046
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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. Abstract : Intracellular aggregation of mutant SOD1 is a major pathological change in ALS. In vitro SOD1 fibrillar aggregates seed aggregation of endogenous SOD1 in cells. Seeded aggregation of mutant SOD1 may describe propagation of SOD1 pathology in ALS.