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Title: Characterization of insulin-degrading enzyme-mediated cleavage of A beta in distinct aggregation states
Authors: Hubin, Ellen ×
Cioffi, Federica
Rozenski, Jef
van Nuland, Nico A. J
Broersen, Kerensa #
Issue Date: 2016
Publisher: Elsevier
Series Title: Biochimica et Biophysica Acta. General Subjects vol:1860 issue:6 pages:1281-1290
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 Met35–Val36 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.
ISSN: 0304-4165
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
× corresponding author
# (joint) last author

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