NR ACVJ
AU Come,J.H.; Fraser,P.E.; Lansbury,P.T.Jr.
TI A kinetic model for amyloid formation in the prion diseases: importance of seeding.
QU Proceedings of the National Academy of Sciences of the United States of America 1993 Jul 1; 90(13): 5959-63
PT journal article
AB The transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases characterized by amyloid formation in the brain. The major amyloid protein is the prion protein (PrP). PrP and the beta-amyloid protein of Alzheimer disease share a similar sequence that, in both cases, may be responsible for the initiation of protein aggregation in vivo. We report here that a peptide based on this sequence in PrP (PrP96-111M) forms amyloid fibrils. The existence of a kinetic barrier to amyloid formation by this peptide was demonstrated, suggesting that formation of an ordered nucleus is the rate-determining step for aggregation. Seeding was demonstrated to occur with PrP96-111M amyloid fibrils but not with amyloid fibrils of a related peptide. This effect is consistent with the proposal that the aggregation of PrP, which characterizes TSE, involves a nucleation event analogous to the seeding of a crystallization.
IN Das Prionprotein und das Alzheimer-typische beta-Amyloid-Protein scheinen eine Sequenzhomologie im Bereich PrP 96-111 zu besitzen.
MH Alzheimer Disease/metabolism; Amino Acid Sequence; Amyloid/*biosynthesis/chemistry; Human; Models, Biological; Molecular Sequence Data; Peptide Fragments/chemistry; Prion Diseases/*metabolism; Prions/metabolism; Support, Non-U.S. Gov't; Thermodynamics; Virus Replication
AD Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.
SP englisch
PO USA
OR Prion-Krankheiten C