Neprilysin (NEP), also known as neutral endopeptidase, is a Zn-dependent metalloprotease which degrades small secreted peptides like the beta-amyloid peptide, tachykinin, neurotensin and enkephalins.[1][2][3][4][5][6][7][8] Its signalling has also been implicated in cardiovascular disease.[9] NEP turns off peptide signalling events at the cell surface. NEP is found in brain tissue and is an integral membrane protein.
3D structures of neprilysin
1dmt – hNEP extracellular domain + phosphoramidon – human
1r1h, 1r1i, 1r1j, 1y8j, 2qpj, 2yb9 - hNEP extracellular domain + inhibitor
2yvc – NEP cytoplasmic tail + radixin - mouse
References
- ↑ Skidgel RA, Erdos EG. Angiotensin converting enzyme (ACE) and neprilysin hydrolyze neuropeptides: a brief history, the beginning and follow-ups to early studies. Peptides. 2004 Mar;25(3):521-5. PMID:15134871 doi:http://dx.doi.org/10.1016/j.peptides.2003.12.010
- ↑ Ouimet T. Neprilysin 2: a novel messenger peptide-inactivating metalloprotease. Protein Pept Lett. 2004 Oct;11(5):479-89. PMID:15544569
- ↑ Hui KS. Brain-specific aminopeptidase: from enkephalinase to protector against neurodegeneration. Neurochem Res. 2007 Dec;32(12):2062-71. Epub 2007 May 3. PMID:17476590 doi:http://dx.doi.org/10.1007/s11064-007-9356-3
- ↑ Hersh LB, Rodgers DW. Neprilysin and amyloid beta peptide degradation. Curr Alzheimer Res. 2008 Apr;5(2):225-31. PMID:18393807
- ↑ Malito E, Hulse RE, Tang WJ. Amyloid beta-degrading cryptidases: insulin degrading enzyme, presequence peptidase, and neprilysin. Cell Mol Life Sci. 2008 Aug;65(16):2574-85. doi: 10.1007/s00018-008-8112-4. PMID:18470479 doi:http://dx.doi.org/10.1007/s00018-008-8112-4
- ↑ Nalivaeva NN, Turner AJ. The amyloid precursor protein: a biochemical enigma in brain development, function and disease. FEBS Lett. 2013 Jun 27;587(13):2046-54. doi: 10.1016/j.febslet.2013.05.010. Epub , 2013 May 16. PMID:23684647 doi:http://dx.doi.org/10.1016/j.febslet.2013.05.010
- ↑ Saido TC. Metabolism of amyloid beta peptide and pathogenesis of Alzheimer's disease. Proc Jpn Acad Ser B Phys Biol Sci. 2013;89(7):321-39. PMID:23883611
- ↑ Grimm MO, Mett J, Stahlmann CP, Haupenthal VJ, Zimmer VC, Hartmann T. Neprilysin and Abeta Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer's Disease. Front Aging Neurosci. 2013 Dec 23;5:98. doi: 10.3389/fnagi.2013.00098. PMID:24391587 doi:http://dx.doi.org/10.3389/fnagi.2013.00098
- ↑ Segura J, Ruilope LM. Dual-acting angiotensin receptor-neprilysin inhibition. Curr Hypertens Rep. 2011 Feb;13(1):74-8. doi: 10.1007/s11906-010-0166-7. PMID:21046489 doi:http://dx.doi.org/10.1007/s11906-010-0166-7
