Characterization of insulin-degrading enzyme-mediated cleavage of Aβ in distinct aggregation states.

TitleCharacterization of insulin-degrading enzyme-mediated cleavage of Aβ in distinct aggregation states.
Publication TypeJournal Article
Year of Publication2016
AuthorsHubin, E., F. Cioffi, J. Rozenski, N. A. J. van Nuland, and K. Broersen
JournalBiochim Biophys Acta
Volume1860
Issue6
Pagination1281-90
Date Published2016 Jun
ISSN0006-3002
KeywordsAmino Acid Sequence, Amyloid beta-Peptides, Insulysin, Molecular Sequence Data, Protein Aggregates
Abstract

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.
DOI10.1016/j.bbagen.2016.03.010
Alternate JournalBiochim. Biophys. Acta
PubMed ID26968463
Research group: 
VanNulandGroup