Characterization of Insulin-degrading Enzyme-mediated Cleavage of Aβ in Distinct Aggregation States
Hubin et al., Biochim Biophys Acta. (2016) - PMID: 26968463
Product(s) used in this publication: Amyloid Beta A4 Peptides
To enhance our understanding of the potential therapeutic utility of insulin-degrading enzyme (IDE) in Alzheimer's disease (AD), we studied in vitro IDE-mediated degradation of different amyloid-beta (Aβ) peptide aggregation states. Our findings show that IDE activity is driven by the dynamic equilibrium between Aβ monomers and higher ordered aggregates. We identify Met(35)-Val(36) as a novel IDE cleavage site in the Aβ sequence and show that Aβ fragments resulting from IDE cleavage form non-toxic amorphous aggregates. These findings need to be taken into account in therapeutic strategies designed to increase Aβ clearance in AD patients by modulating IDE activity.
Copyright © 2016 Elsevier B.V. All rights reserved.
Aggregation; Alzheimer's disease; Amyloid-beta; Aβ cleavage; Insulin-degrading enzyme; Neprilysin