Affinage

MME

Neprilysin · UniProt P08473

Length
750 aa
Mass
85.5 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MME (neprilysin/CD10) is a type II integral membrane zinc metalloendopeptidase of the M13 family that terminates bioactive peptide signaling by cleaving substrates including enkephalins, atrial natriuretic peptide, amyloid-β, CGRP, and mitogenic neuropeptides at the cell surface (PMID:9141502, PMID:12067222, PMID:15963503, PMID:1833101). Its enzymatic activity is required for PMA-induced growth arrest in T cells, maintenance of the mammary stem/progenitor cell niche, and suppression of cancer metastasis through inhibition of FAK-RhoA signaling (PMID:9285485, PMID:20506111, PMID:31054987). MME associates with tetraspanin CD9, which directs its release on exosomes and thereby redistributes peptidase activity to extracellular compartments, and its expression is epigenetically regulated by promoter CpG methylation and lncRNA XIST/EZH2-mediated H3K27me3 deposition (PMID:23289620, PMID:35098860, PMID:24756894). Loss-of-function mutations in MME cause fetomaternal alloimmune membranous glomerulonephritis and late-onset autosomal-dominant axonal polyneuropathies (CMT2) (PMID:15464186, PMID:27588448).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1991 Medium

    Establishing the enzymology: NEP was shown to be the principal degradative enzyme for atrial natriuretic peptide in kidney, with regionally graded activity inhibitable by specific metallopeptidase inhibitors, linking a defined enzymatic activity to organ-level peptide catabolism.

    Evidence Fluorimetric enzymatic assay with specific inhibitors (thiorphan, phosphoramidon) across kidney subregions

    PMID:1833101

    Open questions at the time
    • Substrate selectivity versus other renal peptidases not quantified
    • In vivo functional consequences of renal NEP inhibition not tested
  2. 1997 High

    NEP was characterized as a broad-spectrum type II membrane zinc metalloendopeptidase (M13 family) that terminates signaling by cleaving diverse bioactive peptides including enkephalins and natriuretic peptides, establishing its identity as a general peptide-inactivating ectoenzyme.

    Evidence Biochemical characterization, structural homology analysis, substrate hydrolysis assays, and inhibitor (phosphoramidon) studies across multiple labs

    PMID:11223883 PMID:9141502

    Open questions at the time
    • Full structural basis for substrate recognition not resolved at atomic level at this time
  3. 1997 High

    The catalytic activity of CD10/NEP was shown to be essential for a cellular phenotype — PMA-induced growth arrest in T cells — by demonstrating that catalytically inactive mutant CD10 failed to rescue arrest while wild-type did, moving beyond substrate cataloguing to functional biology.

    Evidence Transfection of wild-type vs. active-site-mutant CD10 into CD10-deficient Jurkat clones, proliferation and DNA fragmentation assays

    PMID:1396581 PMID:9285485

    Open questions at the time
    • Endogenous peptide substrate mediating growth arrest not identified
    • Downstream signaling pathway linking peptide cleavage to cell cycle arrest unknown
  4. 2001 High

    NEP was identified as a major amyloid-β-degrading enzyme, cleaving both Aβ(1-40) and Aβ(1-42) in vitro and in vivo, providing a mechanistic link between NEP activity and Alzheimer's disease pathology.

    Evidence In vitro peptide cleavage assays and in vivo studies with NEP-specific inhibitors (thiorphan, phosphoramidon)

    PMID:12067222

    Open questions at the time
    • Relative contribution of NEP versus other Aβ-degrading enzymes (IDE, ECE) in human brain not quantified
    • Whether NEP upregulation is sufficient to prevent amyloid plaque formation in humans untested
  5. 2004 High

    Truncating MME mutations were shown to cause complete loss of NEP protein on granulocytes and podocytes, leading to maternal alloimmunization against fetal NEP and antenatal membranous glomerulonephritis — the first Mendelian disease linked to MME loss-of-function.

    Evidence Genomic sequencing, SNP haplotyping, Western blot for anti-NEP IgG subclasses, replicated across multiple families

    PMID:15464186

    Open questions at the time
    • Whether partial loss-of-function alleles also provoke alloimmunization unknown
    • Frequency of MME null alleles in general population not established
  6. 2005 High

    NEP was established as the major CGRP-degrading enzyme in human skin, directly linking its peptidase activity to neurogenic inflammation control in vivo.

    Evidence Intracutaneous microdialysis with specific inhibitors (phosphoramidon), laser Doppler imaging of neurogenic flare, CGRP EIA

    PMID:15963503

    Open questions at the time
    • Whether other skin peptidases partially compensate for NEP inhibition not resolved
  7. 2010 Medium

    Two studies expanded MME's roles: enzymatic activity was shown to maintain mammary stem/progenitor cells in an undifferentiated state, and a nonsynonymous variant (Val73) was shown to undergo proteasome/autophagy-mediated degradation due to misfolding, reducing activity to 21% of wild-type.

    Evidence FACS sorting/sphere assays with CD10 inhibition for mammary stem cells; expression constructs in COS-1 cells with enzyme activity assays, proteasome/autophagy inhibitor studies, and chaperone upregulation analysis for the Val73 variant

    PMID:20506111 PMID:20692264

    Open questions at the time
    • Endogenous peptide substrate in mammary niche not identified
    • In vivo relevance of Val73 variant to cardiovascular or neurological phenotypes not established
    • Whether other M13 family members compensate in mammary tissue unknown
  8. 2013 High

    CD9 tetraspanin was identified as a selective physical partner that redirects NEP from the cell surface to exosomes, enhancing exosomal NEP release ~5-fold without altering enzymatic activity, revealing a mechanism for redistributing peptidase activity to extracellular microenvironments.

    Evidence Co-immunoprecipitation, CD9 chimera/mutagenesis, shRNA knockdown, exosome isolation, fluorometric peptidase assay

    PMID:23289620

    Open questions at the time
    • Functional consequence of exosomal NEP on recipient cells not demonstrated
    • Whether CD9-NEP interaction is tissue-specific unknown
  9. 2016 High

    Heterozygous loss-of-function and missense MME mutations were linked to late-onset axonal polyneuropathy (CMT2), with impaired enzymatic activity and reduced tissue protein, establishing a second Mendelian disease caused by MME deficiency.

    Evidence Whole-exome/Sanger sequencing, nerve pathology, tissue neprilysin activity assays across 19 index cases

    PMID:27588448

    Open questions at the time
    • Peptide substrate whose accumulation causes axonal degeneration not identified
    • Mechanism of age-dependent incomplete penetrance not explained
  10. 2019 Medium

    MME was shown to suppress cancer metastasis through a non-canonical mechanism — inhibiting FAK phosphorylation and disrupting FAK-RhoA signaling — extending its function beyond peptide catabolism to regulation of cell adhesion and motility, and active NEP was found on circulating placental extracellular vesicles with elevated levels in preeclampsia.

    Evidence Overexpression/knockdown in ESCC cells with migration/invasion assays, FAK/RhoA Western blots, xenograft models; syncytiotrophoblast vesicle isolation with flow cytometry and fluorometric NEP assays

    PMID:30929513 PMID:31054987

    Open questions at the time
    • Whether FAK inhibition is mediated by peptide cleavage or a direct protein interaction is unresolved
    • Causal role of vesicle-bound NEP in preeclampsia pathogenesis not demonstrated
    • FAK-RhoA finding from single lab
  11. 2022 Medium

    Epigenetic silencing of NEP was mechanistically dissected: lncRNA XIST recruits EZH2 to the NEP promoter to deposit H3K27me3, repressing expression; this complements earlier findings that promoter CpG hypermethylation also silences NEP, establishing dual epigenetic control of NEP transcription.

    Evidence RIP for XIST-EZH2 binding, ChIP for H3K27me3 at NEP promoter, XIST knockdown rescue experiments; bisulfite sequencing of NEP promoter CpG methylation

    PMID:24756894 PMID:35098860

    Open questions at the time
    • Whether XIST-mediated repression is tissue-specific or universal unknown
    • Relationship between CpG methylation and H3K27me3 at the NEP promoter not integrated
    • In vivo relevance of XIST-NEP axis to Alzheimer's pathology not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the identity of the endogenous peptide substrates whose accumulation drives axonal degeneration in CMT2; whether the FAK-RhoA suppression by MME is mediated through peptide cleavage or direct protein interaction; and the physiological significance of exosomal NEP activity on target cells.
  • Neuropathy-causing substrate not identified
  • Structural basis of FAK-RhoA regulation by MME unresolved
  • Functional impact of exosomal NEP on recipient cell signaling not demonstrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 8 GO:0140096 catalytic activity, acting on a protein 4
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 2 GO:0005576 extracellular region 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2
Partners
CD9EZH2FAKHSPA1AHSPB1

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 MME/NEP (neutral endopeptidase-24.11) is a type II integral membrane zinc metallopeptidase (M13 family) that hydrolyzes a wide range of biologically active peptide substrates at the cell surface, including enkephalins and atrial natriuretic peptides, functioning as a thermolysin-like endopeptidase to terminate peptide signaling. Biochemical characterization, structural homology analysis, substrate hydrolysis assays, inhibitor studies (phosphoramidon) FASEB journal High 11223883 9141502
2001 NEP degrades both Aβ(1-40) and Aβ(1-42) in vitro and in vivo, and this catabolism is blocked by NEP-specific inhibitors (thiorphan, phosphoramidon), establishing NEP as a key amyloid-degrading enzyme. In vitro peptide cleavage assays, in vivo animal studies with NEP inhibitors, enzyme inhibitor studies Journal of neurochemistry High 12067222
2004 Truncating mutations (nonsense and frameshift) in the MME gene result in absence of NEP protein on granulocytes and podocytes, leading to maternal alloimmunization against fetal NEP antigen on glomerular podocytes and antenatal membranous glomerulonephritis; IgG subclass analysis confirmed anti-NEP activity. Direct sequencing of genomic PCR products, SNP analysis, Western blotting for IgG subclasses with anti-NEP activity Lancet High 15464186
1992 Jurkat T cells express a functional NEP/CD10 endopeptidase activity (CALLA-related) that cleaves the substrate Suc-Ala-Ala-Phe-pNA; this activity is inhibited by specific endopeptidase 24.11 inhibitors and immunoprecipitated by anti-CD10 monoclonal antibodies, demonstrating that T lymphocytes express functional NEP involved in T cell activation. Enzymatic substrate hydrolysis assays with specific inhibitors, anti-CD10 immunoprecipitation, HPLC analysis of cleavage products, FACS, mRNA analysis The EMBO journal High 1396581
1997 The enzymatic activity of CD10/NEP is required for PMA-induced growth arrest in Jurkat T cells; transfection of an enzymatically inactive form of CD10 into CD10-deficient PMA-resistant clones failed to restore growth arrest, whereas transfection of functional CD10 rescued this phenotype. Transfection of wild-type vs. catalytically inactive CD10 into mutant Jurkat clones, proliferation assays, DNA fragmentation assays FASEB journal High 9285485
1994 CD10/NEP modulates peptide-mediated proliferation in non-small cell lung carcinomas; cells with low CD10/NEP expression grew more rapidly when CD10/NEP was inhibited, and CD10/NEP expression was inversely correlated with PCNA-positive (actively dividing) cells, demonstrating that CD10/NEP suppresses peptide-driven proliferation by degrading mitogenic peptide substrates. CD10/NEP immunostaining, PCNA staining, cell growth inhibition assays with CD10/NEP inhibitors, receptor expression analysis Journal of Clinical Investigation Medium 7962523
2013 Tetraspanin CD9 selectively associates with MME/CD10 at the cell surface; the large extracellular loop (CCG motif to TM4) and C-terminal tail of CD9 mediate this interaction; CD9 co-expression enhances CD10 release on exosomes ~5-fold without altering its enzymatic activity, redistributing NEP peptidase activity from the cell surface to extracellular microenvironments. Co-immunoprecipitation, chimera construction, site-directed mutagenesis of CD9, shRNA knockdown of CD9, exosome isolation, fluorometric peptidase activity assay The FEBS journal High 23289620
2010 MME/CD10 protease activity (and beta1-integrin adhesion) are required to prevent differentiation of mammary progenitor/stem cells; CD10-high/EpCAM-low cells are enriched for early common progenitors and mammosphere-forming cells; inhibition of CD10 enzymatic activity promotes differentiation, demonstrating that CD10-mediated cleavage of signaling peptides maintains the mammary stem cell niche. FACS sorting for CD10/EpCAM, sphere formation assays, CD10 enzymatic inhibition studies, lineage progression in vitro assay Stem cells Medium 20506111
2016 Rare heterozygous loss-of-function and missense mutations in MME result in strongly decreased tissue availability of neprilysin protein and impaired enzymatic activity, causing late-onset autosomal-dominant axonal polyneuropathies (CMT2); mutations segregate with age-related incomplete penetrance. Whole-exome sequencing, Sanger sequencing, nerve pathology, tissue neprilysin activity assays, protein level quantification American journal of human genetics High 27588448
2010 A nonsynonymous MME variant (Val73 allozyme) displays a significant reduction in enzyme activity (21% of wild-type) and immunoreactive protein (29% of wild-type); this variant undergoes proteasome-mediated degradation and autophagy, with upregulation of chaperones BiP and GRP94 suggesting protein misfolding, consistent with the MME X-ray crystal structure. Resequencing, expression constructs in COS-1 cells, quantitative Western blot, one-step fluorometric enzyme assay, inhibitor studies for proteasome/autophagy pathways, chaperone upregulation analysis Journal of molecular and cellular cardiology High 20692264
2019 MME suppresses metastasis of esophageal squamous cell carcinoma by inhibiting phosphorylation of FAK and disrupting the FAK-RhoA signaling axis; MME overexpression also interrupts tumor cell adhesion, demonstrating a mechanistic role for MME in cell movement regulation beyond peptide catabolism. MME overexpression/knockdown in ESCC cells, in vitro migration and invasion assays, in vivo xenograft models, Western blot for FAK phosphorylation and RhoA activity, cell adhesion assays The American journal of pathology Medium 31054987
2019 NEP (neprilysin) is present on syncytiotrophoblast-derived extracellular vesicles (microvesicles and exosomes) in enzymatically active form; NEP activity on these vesicles is inhibited by the specific inhibitor thiorphan, and vesicle-bound NEP levels are significantly elevated in preeclampsia, indicating that circulating placenta-derived vesicles carry active NEP into the maternal circulation. Immunostaining, Western blotting, antibody-coated magnetic bead isolation, flow cytometry, size-exclusion chromatography, fluorometric NEP activity assay with thiorphan inhibition Hypertension High 30929513
2005 NEP (neutral endopeptidase) degrades CGRP in human skin; inhibition of NEP with phosphoramidon increased neurogenic flare intensity and size and enabled CGRP detection in microdialysis samples, establishing NEP as the major enzyme responsible for CGRP degradation in neurogenic inflammation. Intracutaneous microdialysis with specific inhibitors (phosphoramidon for NEP, captopril for ACE), laser Doppler imaging, CGRP EIA Experimental neurology High 15963503
2008 Human NEP2 (neprilysin-2, homologous to MME/NEP) exists as a membrane-bound and soluble enzyme with distinct subcellular localization (ER and plasma membrane glycoforms) and displays distinct substrate specificity and inhibitor binding compared to NEP, suggesting non-redundant physiological roles. Cloning and expression of human NEP2 isoforms, subcellular fractionation, substrate specificity assays, inhibitor binding studies FEBS letters Medium 18539150
2007 HSP27 and HSP70 interact with CD10/MME in C4-2 prostate cancer cells, identified by immunoprecipitation of CD10-protein complexes followed by mass spectrometry; the interaction was confirmed by reciprocal immunopurification with anti-HSP27 and anti-HSP70 antibodies. Immunoprecipitation with anti-CD10 antibody, microLC-ESI-MS/MS proteomics, Western blot confirmation, reciprocal immunoprecipitation The Prostate Medium 17342744
2022 lncRNA XIST represses NEP expression by recruiting EZH2 to the NEP promoter, leading to H3K27me3 enrichment at the promoter; XIST knockdown restores NEP expression and alleviates Aβ-induced neuronal inflammation and damage. RIP (RNA immunoprecipitation) to validate XIST-EZH2 binding, ChIP to confirm H3K27me3 enrichment at NEP promoter, Western blot, qRT-PCR, ELISA, TUNEL assay Journal of neurogenetics Medium 35098860
2019 CD10 expression in adventitial perivascular cells increases their proliferation and osteogenic differentiation; CD10+ cells activate CCND2 via ERK1/2 signaling and osteoblastogenic gene expression via NF-κB signaling; CD10 expression in these cells is upregulated through sonic hedgehog-mediated GLI1 signaling. FACS sorting, proliferation and clonogenic assays, osteogenic differentiation assays, Western blot for ERK1/2 and NF-κB pathway components, gene expression analysis Stem cells Medium 31721342
1991 NEP (neutral metalloendopeptidase EC 3.4.24.11) is the major degradative enzyme for atrial natriuretic peptide (ANP) in the kidney; NEP activity is 18-fold higher in the outer stripe of the medulla than in the outer cortex, with the highest activity in juxtamedullary proximal tubules; activity is specifically inhibited by NEP inhibitors SCH39370, phosphoramidon, and thiorphan at micromolar concentrations. Enzymatic fluorimetric activity assay with synthetic substrate, regional kidney fractionation, specific inhibitor studies Clinical and experimental pharmacology & physiology Medium 1833101
2014 CpG sites in the NEP gene promoter are hypermethylated in N2a neuroblastoma cells expressing APP; curcumin treatment induces CpG demethylation at the NEP promoter to restore NEP expression, and NEP upregulation is associated with inhibition of AKT and subsequent suppression of NF-κB and downstream inflammatory targets (COX-2, iNOS). Bisulfite-sequencing PCR (BSP) assay for CpG methylation, Western blot for NEP/AKT/NF-κB pathway proteins, pharmacological treatment with curcumin The AAPS journal Medium 24756894

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 CD10+GPR77+ Cancer-Associated Fibroblasts Promote Cancer Formation and Chemoresistance by Sustaining Cancer Stemness. Cell 997 29395328
1997 Mammalian membrane metallopeptidases: NEP, ECE, KELL, and PEX. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 344 9141502
2001 The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function. BioEssays : news and reviews in molecular, cellular and developmental biology 333 11223883
2017 Mature CD10+ and immature CD10- neutrophils present in G-CSF-treated donors display opposite effects on T cells. Blood 265 28053192
2002 Neoplastic T cells in angioimmunoblastic T-cell lymphoma express CD10. Blood 253 11781247
2002 Beta-amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases? Journal of neurochemistry 207 12067222
2023 Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial. The Lancet. Oncology 162 38039991
2002 Properties of a fetal multipotent neural stem cell (NEP cell). Developmental biology 149 12435354
2011 Concise review: neutral endopeptidase (CD10): a multifaceted environment actor in stem cells, physiological mechanisms, and cancer. Stem cells (Dayton, Ohio) 148 21425402
2004 Role of truncating mutations in MME gene in fetomaternal alloimmunisation and antenatal glomerulopathies. Lancet (London, England) 144 15464186
2012 Emerging roles for the influenza A virus nuclear export protein (NEP). PLoS pathogens 131 23236273
2013 Neprilysin and Aβ Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer's Disease. Frontiers in aging neuroscience 124 24391587
2002 CD10 is a marker for normal and neoplastic endometrial stromal cells. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 119 11781522
2023 Immunosuppressive CD10+ALPL+ neutrophils promote resistance to anti-PD-1 therapy in HCC by mediating irreversible exhaustion of T cells. Journal of hepatology 94 37689322
2019 Placental Syncytiotrophoblast-Derived Extracellular Vesicles Carry Active NEP (Neprilysin) and Are Increased in Preeclampsia. Hypertension (Dallas, Tex. : 1979) 91 30929513
2013 Tetraspanin protein CD9 interacts with metalloprotease CD10 and enhances its release via exosomes. The FEBS journal 91 23289620
1994 Leukemia-associated changes identified by quantitative flow cytometry: I. CD10 expression. Cytometry 87 7895527
2008 Differential cerebral deposition of IDE and NEP in sporadic and familial Alzheimer's disease. Neurobiology of aging 75 19019493
1993 Clinical significance of CD10 expression in childhood acute lymphoblastic leukemia. Leukemia 71 8418377
2003 B-cell lymphomas with coexpression of CD5 and CD10. American journal of clinical pathology 70 12579992
1983 Expression of common acute lymphoblastic leukemia antigen (CALLA) on human malignant melanoma cell lines. Journal of immunology (Baltimore, Md. : 1950) 70 6339629
2010 The CD10 enzyme is a key player to identify and regulate human mammary stem cells. Stem cells (Dayton, Ohio) 67 20506111
1993 NEP: a novel receptor-like tyrosine kinase expressed in proliferating neuroepithelia. Oncogene 64 8397369
2007 Immunohistochemical staining of CD10 in atypical fibroxanthomas. Journal of cutaneous pathology 63 17448198
2004 CD10 expression in extranodal dissemination of angioimmunoblastic T-cell lymphoma. The American journal of surgical pathology 62 14707864
2004 Expression of CD10 in basal cell carcinoma. The American Journal of dermatopathology 61 15618927
1994 CD10/NEP in non-small cell lung carcinomas. Relationship to cellular proliferation. The Journal of clinical investigation 56 7962523
1992 Jurkat T cells express a functional neutral endopeptidase activity (CALLA) involved in T cell activation. The EMBO journal 56 1396581
1983 Distribution and modulation of a human leukemia-associated antigen (CALLA). Journal of immunology (Baltimore, Md. : 1950) 54 6225802
2004 The ectopeptidases CD10, CD13, CD26, and CD143 are upregulated in gastric cancer. International journal of oncology 53 15492809
2001 Decreased CD10 expression in grade III and in interfollicular infiltrates of follicular lymphomas. American journal of clinical pathology 53 11392883
1992 Induction of isotype switching and Ig production by CD5+ and CD10+ human fetal B cells. Journal of immunology (Baltimore, Md. : 1950) 53 1375243
2007 Differential expression of CD10 in prostate cancer and its clinical implication. BMC urology 52 17335564
2002 Expression of CD10 in malignant müllerian mixed tumors and adenosarcomas: an immunohistochemical study. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 52 12218209
1986 Structure/function studies of the common acute lymphoblastic leukemia antigen (CALLA/CD10) expressed on human neutrophils. Journal of immunology (Baltimore, Md. : 1950) 52 2941484
2001 Influenza B and C virus NEP (NS2) proteins possess nuclear export activities. Journal of virology 49 11462009
2001 Influenza A virus NEP (NS2 protein) downregulates RNA synthesis of model template RNAs. Journal of virology 48 11312364
2016 Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies. American journal of human genetics 47 27588448
1985 Expression of the common acute lymphoblastic leukaemia antigen (CALLA gp100) in the brush border of normal jejunum and jejunum of patients with coeliac disease. Journal of clinical pathology 47 2931454
2022 lncRNA XIST induces Aβ accumulation and neuroinflammation by the epigenetic repression of NEP in Alzheimer's disease. Journal of neurogenetics 46 35098860
2008 Gene cloning and heterologous synthesis of a haloalkaliphilic extracellular protease of Natrialba magadii (Nep). Extremophiles : life under extreme conditions 46 18553052
2005 Inhibition of neutral endopeptidase (NEP) facilitates neurogenic inflammation. Experimental neurology 46 15963503
2005 Stromal CD10 expression in mammary fibroadenomas and phyllodes tumours. Journal of clinical pathology 45 15677540
2005 CD5, CD10, and CD23 expression in Waldenstrom's macroglobulinemia. Clinical lymphoma 45 15794857
2013 The Expression of CD10 and CD15 Is Progressively Increased during Colorectal Cancer Development. Korean journal of pathology 43 24009629
2008 Mantle cell lymphoma with aberrant expression of CD10. Histopathology 43 18518902
2012 EGFR, CD10 and proliferation marker Ki67 expression in ameloblastoma: possible role in local recurrence. Diagnostic pathology 42 22300665
1992 The increase of low density subpopulations and CD10 (CALLA) negative neutrophils in severely infected patients. Surgery today 39 1392343
2014 Curcumin inhibits the AKT/NF-κB signaling via CpG demethylation of the promoter and restoration of NEP in the N2a cell line. The AAPS journal 37 24756894
2020 LncRNA ANRIL Silencing Alleviates High Glucose-Induced Inflammation, Oxidative Stress, and Apoptosis via Upregulation of MME in Podocytes. Inflammation 36 32617859
2019 CD10 expression identifies a subset of human perivascular progenitor cells with high proliferation and calcification potentials. Stem cells (Dayton, Ohio) 36 31721342
2003 Analysis of CD10+ hairy cell leukemia. American journal of clinical pathology 35 12931553
1993 Expression of CALLA/CD10 on human melanoma cells. Melanoma research 34 8292887
2019 Deep learning based topology guaranteed surface and MME segmentation of multiple sclerosis subjects from retinal OCT. Biomedical optics express 33 31646029
1995 Expression of membrane-bound peptidases (CD10 and CD26) on human articular chondrocytes. Possible role of neuropeptidases in the pathogenesis of osteoarthritis. Clinical and experimental rheumatology 31 7656459
2001 Long lasting antinociceptive properties of enkephalin degrading enzyme (NEP and APN) inhibitor prodrugs. Journal of medicinal chemistry 29 11585456
2020 The genetic landscape of axonal neuropathies in the middle-aged and elderly: Focus on MME. Neurology 27 33144514
2019 Membrane Metalloendopeptidase (MME) Suppresses Metastasis of Esophageal Squamous Cell Carcinoma (ESCC) by Inhibiting FAK-RhoA Signaling Axis. The American journal of pathology 27 31054987
2007 Clinical relevance of neutral endopeptidase (NEP/CD10) in melanoma. Journal of translational medicine 26 17207277
2023 Ferroptosis of CD163+ tissue-infiltrating macrophages and CD10+ PC+ epithelial cells in lupus nephritis. Frontiers in immunology 25 37583695
2010 Natriuretic peptide pharmacogenetics: membrane metallo-endopeptidase (MME): common gene sequence variation, functional characterization and degradation. Journal of molecular and cellular cardiology 25 20692264
2008 Human neprilysin-2 (NEP2) and NEP display distinct subcellular localisations and substrate preferences. FEBS letters 25 18539150
2004 Expression of CD13/aminopeptidase N and CD10/neutral endopeptidase on cultured human keratinocytes. Immunology letters 25 14757368
1998 Human cytomegalovirus infection downregulates expression of the cellular aminopeptidases CD10 and CD13. Virology 23 9792845
2004 CD10 expression in diffuse large B-cell lymphomas does not influence survival. Virchows Archiv : an international journal of pathology 22 15517363
1997 Endopeptidase 24.11 (CD10/NEP) is required for phorbol ester-induced growth arrest in Jurkat T cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 22 9285485
2022 Ginsenoside F1 Protects the Brain against Amyloid Beta-Induced Toxicity by Regulating IDE and NEP. Life (Basel, Switzerland) 21 35054451
2021 Low-density neutrophils in chronic graft versus host disease (cGVHD) are primarily immature CD10- and enhance T cell activation. Clinical and experimental immunology 21 33932293
2018 Characterising the phenotype and mode of inheritance of patients with inherited peripheral neuropathies carrying MME mutations. Journal of medical genetics 21 30415211
2010 NEP-like endopeptidases and Alzheimer's disease [corrected]. Current Alzheimer research 21 20088804
2007 CD10 expression in tumour and stromal cells of bladder carcinoma: an association with bilharziasis. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 21 18092952
2017 Screening of genetic variants in ADCYAP1R1, MME and 14q21 in a Swedish cluster headache cohort. The journal of headache and pain 20 28831700
2007 NHERFs, NEP, MAGUKs, and more: interactions that regulate PTEN. Journal of cellular biochemistry 20 17786934
2002 CD10 expression in non-small cell lung cancer. Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology 20 12122282
1989 CD10-(CALLA)-Positive Lymphocytes in Myeloma: Evidence that they are a Malignant Precursor Population and are of Germinal Centre Origin. Leukemia & lymphoma 20 27456402
1987 Multiple myeloma: the relationship between CALLA (CD10) positive lymphocytes in the peripheral blood and light chain isotype suppression. British journal of haematology 20 2959309
1985 Phenotypic conversion of TdT+ adult AML to CALLA+ ALL. Scandinavian journal of haematology 20 3864234
2019 The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells. International journal of oncology 19 31746375
2011 CD10 expression helps to differentiate basal cell carcinoma from trichoepithelioma. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences 19 22279463
2005 CD10 is expressed in cutaneous clear cell lesions of different histogenesis. Journal of cutaneous pathology 19 15811119
2003 Neutral endopeptidase/CD10 expression in the stroma of epithelial ovarian carcinoma. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 19 12649673
1988 Decreased expression of the common acute lymphoblastic leukaemia antigen (CALLA/CD10) on neutrophils from patients with thermal injury. British journal of haematology 19 2968812
2007 HSP27 and HSP70 interact with CD10 in C4-2 prostate cancer cells. The Prostate 17 17342744
2024 A comprehensive review of the literature on CD10: its function, clinical application, and prospects. Frontiers in pharmacology 16 38389922
2016 CD10 down expression in follicular lymphoma correlates with gastrointestinal lesion involving the stomach and large intestine. Cancer science 16 27513891
2015 Study of Ki67 and CD10 expression as predictive factors of recurrence of ameloblastoma. European annals of otorhinolaryngology, head and neck diseases 16 26386615
2012 Anti-CD10 (56C6) expression in soft tissue sarcomas. Pathology, research and practice 16 22464152
2012 Copy number variation in ACHE/EPHB4 (7q22) and in BCHE/MME (3q26) genes in sporadic breast cancer. Chemico-biological interactions 16 23063927
2005 Triple ACE-ECE-NEP inhibition in heart failure: a comparison with ACE and dual ECE-NEP inhibition. Journal of cardiovascular pharmacology 16 16116347
1987 Identification and characterization of a unique subpopulation (CALLA/CD10/negative) of human neutrophils manifesting a heightened chemotactic response to activated complement. Blood 16 2959334
2015 Mucinous phenotype and CD10 expression of primary adenocarcinoma of the small intestine. World journal of gastroenterology 15 25759539
2003 Dual ACE and NEP inhibitors: a review of the pharmacological properties of MDL 100240. Cardiovascular drug reviews 15 12595917
2002 Role of ACE and NEP in bradykinin-induced relaxation and contraction response of isolated porcine basilar artery. Naunyn-Schmiedeberg's archives of pharmacology 15 12012022
2000 Increased expression of neutral endopeptidase (NEP) and aminopeptidase N (APN) on peripheral blood mononuclear cells in patients with multiple sclerosis. Immunology letters 15 10714440
2010 CD10 (Neutral Endopeptidase) Expression in Myoepithelial Cells of Salivary Neoplasms. Applied immunohistochemistry & molecular morphology : AIMM 14 19752720
2020 Interaction of influenza A virus NS2/NEP protein with the amino-terminal part of Nup214. Turkish journal of biology = Turk biyoloji dergisi 13 32256144
2016 IFR4/MUM1-positive lymphoma in Waldeyer ring with co-expression of CD5 and CD10. Pediatric blood & cancer 13 27616053
1991 Distribution and inhibition of neutral metalloendopeptidase (NEP) (EC 3.4.24.11), the major degradative enzyme for atrial natriuretic peptide, in the rat kidney. Clinical and experimental pharmacology & physiology 13 1833101
2017 Pax8, Napsin A, and CD10 as Immunohistochemical Markers of Canine Renal Cell Carcinoma. Veterinary pathology 12 28346124
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