β-Amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases?
Version of Record online: 25 MAR 2002
Journal of Neurochemistry
Volume 81, Issue 1, pages 1–8, April 2002
How to Cite
Carson, J. A. and Turner, A. J. (2002), β-Amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases?. Journal of Neurochemistry, 81: 1–8. doi: 10.1046/j.1471-4159.2002.00855.x
- Issue online: 25 MAR 2002
- Version of Record online: 25 MAR 2002
- Received November 2, 2001; revised manuscript received January 9, 2002; accepted January 16, 2002.
The steady-state level of amyloid β-peptide (Aβ) represents a balance between its biosynthesis from the amyloid precursor protein (APP) through the action of the β- and γ-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 Aβ1−40 and Aβ1−42in 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 Aβ degradation may provide a novel approach to the therapy of Alzheimer's disease.