MME是一種膜酶，全名為中性粒細胞膜酶。它主要參與蛋白質(zhì)代謝和降解過程，在腫瘤、炎癥、免疫反應等多種生理和病理過程中發(fā)揮重要作用。最近的研究表明，MME在腫瘤轉(zhuǎn)移、神經(jīng)退行性疾病、自身免疫性疾病等多種疾病的發(fā)生和發(fā)展中發(fā)揮著重要作用，成為了一個重要的生物標志物和潛在的治療靶點。

Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids. Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond. Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9. Involved in the degradation of the atrial natriuretic factor (ANF). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers.

1. feeding monohydroxylated demethoxycurcumin (also named demethylcurcumin) or dihydroxylated bisdemethoxycurcumin (also named bisdemethylcurcumin) to APPswe/PS1dE9 double transgenic mice upregulated NEP levels in the brain and reduced Abeta accumulation in the hippocampus and cortex. PMID: 27407064
2. The abundance of elastic fibers was reduced and fragmented in obesity, suggesting that the reduction in elastic fibers is initially caused by increased neprilysin and decreased fibrillin-1 expression, which may inhibit formation and stabilization of elastic fibers, resulting in skin fragility in obesity. PMID: 27892729
3. results indicate that NEP accelerates adipogenesis through enhancement of insulin-mediated PI3K-Akt activation and imply a high therapeutic value of NEP in treating obesity and obesity-related disorders. PMID: 28239754
4. Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies PMID: 27588448
5. Amyloid beta (Abeta)-degrading effects of overexpressed neprilysin can block deleterious BACE1-elevating mechanisms that accelerate Abeta production PMID: 25884928
6. Serum CD10 levels might serve as a useful marker of synchronous and metachronous liver metastasis in colorectal cancer. PMID: 24972738
7. Cell hypoxia in neuroblastoma cells results in up-regulation of neprilysin expression. PMID: 24947680
8. Neprilysin knockout mice developed more severe hyperalgesia than wild-type mice. PMID: 24333776
9. Data indicate that 5-aza-deoxycytidine induced the demethylation of neprilysin (NEP) gene and significantly increased NEP expression in a dose-dependent manner. PMID: 25108432
10. Data indicate an important, previously neglected, role of NEP for regulation of luminal factors in the epididymis and suggest a novel role for CNP/guanylyl cyclase B in the epididymal epithelium. PMID: 24099862
11. exogenous neprilysin was localized mainly in endosomes, thereby effectively excluding Abeta oligomers from the brain. AAV vector-mediated gene transfer may provide a therapeutic strategy for neurodegenerative diseases PMID: 23503602
12. These data suggest that NEP plays an important role in regulating the hair cycle by its increased expression and activity in the follicular epithelium during early anagen. PMID: 23418484
13. Data suggest that neprilysin (NEP) is up-regulated with chronic exposure of islet beta cells to free fatty acid and leads to insulin secretory dysfunction; in knockout mice, lack of NEP protects against high-fat induced insulin secretory dysfunction. PMID: 23328128
14. Genetic deficiency in neprilysin in conjunction with physiological stress initiate excessive alcohol consumption in mice. PMID: 23185571
15. Cell surface expression of the major amyloid-beta peptide (Abeta)-degrading enzyme, neprilysin, depends on phosphorylation by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) and dephosphorylation by protein phosphatase 1a. PMID: 22767595
16. hypoxia may down-regulate NEP by increasing H3K9me2 and decreasing H3-Ace modulation PMID: 21559427
17. In this study, neutral endopeptidase played a role in regulating nerve function in insulin-deficient diabetes and obesity. PMID: 20849865
18. in vivo findings suggest that loss of NEP in mice could cause increased susceptibility to injury or exacerbate inflammatory responses after diesel exhaust particles exposure via release of specific cytokines from the lungs PMID: 21877416
19. NEP is a crucial player in the development of obesity. PMID: 20862277
20. Both VIP and NEP were predominantly localized to the columnar epithelia of the airways in naive lungs. NEP localization in the columnar epithelia decreased after allergen challenge. PMID: 20566347
21. a soluble secreted form of NEP when circulating in plasma can effectively lower brain Abeta levels and prevent Abeta deposition. PMID: 20558294
22. Divalent copper ions (Cu2+) downregulate neprilysin activity via a proteasome pathway through modulation of neprilysin protein degradation. PMID: 20061635
23. Neprilysin impedes islet amyloid formation by inhibition of fibril formation rather than peptide degradation PMID: 20400513
24. Neprilysin was localized to hippocampal presynaptic terminals. Age-related downregulation of neprilysin may cause increases in synaptic amyloid-beta. PMID: 12074840
25. Decreased neprilysin levels with aging was observed in the mouse hippocampal formation, including the dentate gyrus. Neprilysin was decreased selectively at the terminal zones and on axons of the lateral perforant path and the mossy fibers. PMID: 12391610
26. Decreased expression of neprilysin protein accompanies the age-related accumulation of beta-amyloid peptides in transgenic Tg2576 mouse cerebral cortex and indicates lack of feedback of increasing amount of its substrate on neprilysin expression level. PMID: 12633883
27. an increase of brain NEP levels in aged mice expressing the AD-causing amyloid precursor protein mutations (SwAPP) with pre-existing plaque pathology did not result in significant reduction of plaque pathology PMID: 15043995
28. endogenous targeting signal in wild-type neprilysin is well optimized for the overall neuronal clearance of Abeta PMID: 15100223
29. ANP and AT1 receptor blockade attenuate angiotensin II-induced renomedullary interstitial cells proliferation and extracellular matrix synthesis more efficiently in the absence of neutral endopeptidase. PMID: 16582578
30. Nicastrin deficiency drastically lowers neprilysin expression, membrane-bound activity and mRNA levels. This correlates well with our demonstration of an indirect gamma-secretase-dependent modulation of neprilysin at its transcriptional level. PMID: 16606360
31. reduced neprilysin activity appears to be a causative event that is at least partly responsible for the memory-associated symptoms of Alzheimer disease PMID: 16636059
32. beta-amyloid levels in the brain are regulated by neprilysin and endothelin-converting enzyme but not angiotensin-converting enzyme PMID: 16912050
33. Results provide the evidence that lowering of brain Abeta levels by increasing its degradation can improve cognitive functions in vivo, and suggest that increasing the activity of neprilysin in brain may be effective in preventing cognitive decline. PMID: 17008108
34. activity in skin decreased dramatically soon after skin-scratching stimulation PMID: 17692507
35. NEP is the peptidase degrading mephrin A truncated B-type natriuretic peptide in kidney PMID: 17823376
36. Abeta induces epigenetic effects, implying that DNA methylation may be part of a vicious cycle involving the reduction in neprilysin expression along with a resultant increase in Abeta accumulation, and that Abeta may induce global DNA hypo-methylation. PMID: 19007750
37. findings support the hypothesis of an important role of NEP and its substrates in the pathogenesis of complex regional pain syndrome PMID: 19084065
38. The differential effect of neprilysin on plaques and oligomers suggests that neprilysin-dependent degradation of Abeta affects plaques more than oligomers and that these structures may form through distinct assembly mechanisms. PMID: 19228952
39. endogenous Abeta concentrations were elevated in the brains of NEP-knockout mice at all investigated age groups, immunohistochemical analysis did not detect any Abeta deposits even in old NEP knockout mice PMID: 19240795

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Cell membrane; Single-pass type II membrane protein.

Peptidase M13 family

KEGG: mmu:17380

STRING: 10090.ENSMUSP00000029400

UniGene: Mm.296022