Title | Characterization of insulin-degrading enzyme-mediated cleavage of Aβ in distinct aggregation states. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Hubin, E., F. Cioffi, J. Rozenski, N. A. J. van Nuland, and K. Broersen |
Journal | Biochim Biophys Acta |
Volume | 1860 |
Issue | 6 |
Pagination | 1281-90 |
Date Published | 2016 Jun |
ISSN | 0006-3002 |
Keywords | Amino 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. |
DOI | 10.1016/j.bbagen.2016.03.010 |
Alternate Journal | Biochim. Biophys. Acta |
PubMed ID | 26968463 |
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