Comparative studies for amyloid beta degradation: “Neprilysin vs insulysin”, “monomeric vs aggregate”, and “whole Aβ40 vs its peptide fragments”

Dai Kato, Yoshiaki Takahashi, Haruto Iwata, Yusuke Hatakawa, Seon Hwa Lee, Tomoyuki Oe

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Amyloid beta (Aβ) proteins are produced from amyloid precursor protein cleaved by β- and γ-secretases, and are the main components of senile plaques pathologically found in Alzheimer's disease (AD) patient brains. Therefore, the relationship between AD and Aβs has been well studied for both therapeutic and diagnostic purposes. Several enzymes have been reported to degrade Aβs in vivo, with neprilysin (NEP) and insulysin (insulin-degrading enzyme, IDE) being the most prominent. In this article, we describe the mass spectrometric characterization of peptide fragments generated using NEP and IDE, and clarify the differences in digestion specificities between these two enzymes for non-aggregated Aβ40, aggregated Aβ40, and Aβ40 peptide fragments, including Aβ16. Our results allowed identification of all the peptide fragments from non-aggregated Aβ40: NEP, 23 peptide fragments consisting of 2–11 amino-acid residues, 17 cleavage sites; IDE, 23 peptide fragments consisting of 6–33 amino-acid residues, 15 cleavage sites. Also, we confirmed that IDE can digest only whole Aβ40, whereas NEP can digest both Aβ40 and partial structures such as Aβ16 and peptide fragments generated by the digestion of Aβ40 by IDE. Furthermore, we confirmed that IDE and NEP are unable to digest aggregated Aβ40.

Original languageEnglish
Article number101268
JournalBiochemistry and Biophysics Reports
Publication statusPublished - 2022 Jul


  • Amyloid beta
  • Insulin-degrading enzyme
  • Insulysin
  • Neprilysin


Dive into the research topics of 'Comparative studies for amyloid beta degradation: “Neprilysin vs insulysin”, “monomeric vs aggregate”, and “whole Aβ40 vs its peptide fragments”'. Together they form a unique fingerprint.

Cite this