|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|
|Date Published||2016 Jun|
|Keywords||Amino Acid Sequence, Amyloid beta-Peptides, Insulysin, Molecular Sequence Data, Protein Aggregates|
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.
|Alternate Journal||Biochim. Biophys. Acta|
Characterization of insulin-degrading enzyme-mediated cleavage of Aβ in distinct aggregation states.