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REVIEW: Neutral Endopeptidase (Neprilysin) in Therapy and Diagnostics: Yin and Yang

E. E. Feygina1,2,a*, A. G. Katrukha1,3, and A. G. Semenov1,2

1HyTest Ltd., 20520 Turku, Finland

2Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

3Lomonosov Moscow State University, Faculty of Biology, 119991 Moscow, Russia

* To whom correspondence should be addressed.

Received June 7, 2019; Revised August 2, 2019; Accepted August 19, 2019
Neprilysin (NEP) is a zinc-dependent metalloproteinase that exists in organisms in both transmembrane and soluble forms. NEP substrates are involved in regulating the cardiovascular and nervous systems. In this review, we discuss some of the biochemical characteristics and physiological functions of this enzyme with special emphasis on the use of NEP as a therapeutic target. The history and various physiological aspects of applying NEP inhibitors for treating heart failure and attempts to increase NEP activity when treating Alzheimer’s disease using gene and cell therapies are described. Another important issue discussed is the role of NEP as a potential marker for predicting the risk of cardiovascular disease complications. The diagnostic and prognostic performance of soluble NEP in various types of heart failure is analyzed and presented. We also discuss the methods and approaches for measuring NEP activity for prognosis and diagnosis, as well as a possible new role of natriuretic peptides (NEP substrates) in cardiovascular diagnostics.
KEY WORDS: neprilysin, natriuretic peptides, ARNi, heart failure, Alzheimer’s disease, biomarkers, immunoanalysis

DOI: 10.1134/S0006297919110105