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July 11, 2016
Very Important Paper: The Metalloprotease Neprilysin Degrades and Inactivates Apelin Peptides
Shaun M.K. McKinnie, Conrad Fischer, Kelvin M.H. Tran, Wang Wang, Fabricio Mosquera, Gavin Y. Oudit, John C. Vederas*
The apelinergic system is a mammalian peptide hormone network with key physiological roles. Apelin isoforms and analogues are believed to be promising therapeutics for cardiovascular disease. So far only one protease, angiotensin-converting enzyme 2 (ACE2), had been implicated in its physiological regulation. Through the use of a peptide-based fluorescent probe, J.C. Vederas (University of Alberta, Canada) and co-workers have identified the metalloprotease neprilysin (NEP; a target for Entresto™ used in the treatment of heart failure) as an enzyme that cleaves apelin isoforms. In vitro NEP proteolysis generates fragments without the ability to bind to the apelin receptor, thereby making NEP the first protease known to fully inactivate apelin.
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