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Amyloid‐β Peptide Induces Prion Protein Amyloid Formation: Evidence for Its Widespread Amyloidogenic Effect
Author(s) -
Honda Ryo
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201800197
Subject(s) - amyloid (mycology) , prion protein , peptide , chemistry , amyloid β , amyloid fibril , biophysics , biochemistry , biology , medicine , disease , inorganic chemistry
Transmissible spongiform encephalopathy is associated with misfolding of prion protein (PrP) into an amyloid β‐rich aggregate. Previous studies have indicated that PrP interacts with Alzheimer′s disease amyloid‐β peptide (Aβ), but it remains elusive how this interaction impacts on the misfolding of PrP. This study presents the first in vitro evidence that Aβ induces PrP‐amyloid formation at submicromolar concentrations. Interestingly, systematic mutagenesis of PrP revealed that Aβ requires no specific amino acid sequences in PrP, and induces the misfolding of other unrelated proteins (insulin and lysozyme) into amyloid fibrils in a manner analogous to PrP. This unanticipated nonspecific amyloidogenic effect of Aβ indicates that this peptide might be involved in widespread protein aggregation, regardless of the amino acid sequences of target proteins, and exacerbate the pathology of many neurodegenerative diseases.