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International Journal of Alzheimer’s Disease
Volume 2012 (2012), Article ID 383796, 12 pages
Review Article

The Alzheimer's Amyloid-Degrading Peptidase, Neprilysin: Can We Control It?

1School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
2I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, RAS, 44 Thorez Avenue, Saint Petersburg 194223, Russia

Received 15 February 2012; Accepted 1 June 2012

Academic Editor: Fabrizio Tagliavini

Copyright © 2012 N. N. Nalivaeva et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The amyloid cascade hypothesis of Alzheimer's disease (AD) postulates that accumulation in the brain of amyloid β-peptide (Aβ) is the primary trigger for neuronal loss specific to this pathology. In healthy brain, Aβ levels are regulated by a dynamic equilibrium between Aβ release from the amyloid precursor protein (APP) and its removal by perivascular drainage or by amyloid-degrading enzymes (ADEs). During the last decade, the ADE family was fast growing, and currently it embraces more than 20 members. There are solid data supporting involvement of each of them in Aβ clearance but a zinc metallopeptidase neprilysin (NEP) is considered as a major ADE. NEP plays an important role in brain function due to its role in terminating neuropeptide signalling and its decrease during ageing or after such pathologies as hypoxia or ischemia contribute significantly to the development of AD pathology. The recently discovered mechanism of epigenetic regulation of NEP by the APP intracellular domain (AICD) opens new avenues for its therapeutic manipulation and raises hope for developing preventive strategies in AD. However, consideration needs to be given to the diverse physiological roles of NEP. This paper critically evaluates general biochemical and physiological functions of NEP and their therapeutic relevance.