Beta-amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases?

J Neurochem. 2002 Apr;81(1):1-8. doi: 10.1046/j.1471-4159.2002.00855.x.


The steady-state level of amyloid beta-peptide (Abeta) represents a balance between its biosynthesis from the amyloid precursor protein (APP) through the action of the beta- and gamma-secretases and its catabolism by a variety of proteolytic enzymes. Recent attention has focused on members of the neprilysin (NEP) family of zinc metalloproteinases in amyloid metabolism. NEP itself degrades both Abeta(1-40) and Abeta(1-42) in vitro and in vivo, and this metabolism is prevented by NEP inhibitors. Other NEP family members, for example endothelin-converting enzyme, may contribute to amyloid catabolism and may also play a role in neuroprotection. Another metalloproteinase, insulysin (insulin-degrading enzyme) has also been advocated as an amyloid-degrading enzyme and may contribute more generally to metabolism of amyloid-forming peptides. Other candidate enzymes proposed include angiotensin-converting enzyme, some matrix metalloproteinases, plasmin and, indirectly, thimet oligopeptidase (endopeptidase-24.15). This review critically evaluates the evidence relating to proteinases implicated in amyloid catabolism. Therapeutic strategies aimed at promoting A,beta degradation may provide a novel approach to the therapy of Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Aspartic Acid Endopeptidases / metabolism
  • Endothelin-Converting Enzymes
  • Humans
  • Insulysin / metabolism
  • Metalloendopeptidases / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Neprilysin / metabolism
  • Nervous System / metabolism
  • Peptide Fragments / metabolism


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Peptide Fragments
  • Aspartic Acid Endopeptidases
  • Metalloendopeptidases
  • Neprilysin
  • Insulysin
  • Endothelin-Converting Enzymes