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

Ellen Hubin, Federica Cioffi, Jef Rozenski, Nico A J Van Nuland*, Kerensa Broersen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1281-1290
Number of pages10
JournalBiochimica et biophysica acta. General subjects
Volume1860
Issue number6
DOIs
Publication statusPublished - 1 Jun 2016

Keywords

  • Aggregation
  • Alzheimer's disease
  • Amyloid-beta
  • Aβ cleavage
  • Insulin-degrading enzyme
  • Neprilysin

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