中性エンドペプチダーゼ

関: enkephalinase、neprilysin

同: NEP

WordNet

possessing no distinctive quality or characteristics
one who does not side with any party in a war or dispute
having no net electric charge (同)electroneutral
lacking distinguishing quality or characteristics; "a neutral personality that made no impression whatever"
not supporting or favoring either side in a war, dispute, or contest

PrepTutorEJDIC

『中立の』;中立国の / 『公平な』,不偏不党の / (人・物が)特色のはっきりしない;(色が)はっきりしない,くすんだ / (酸性でもアルカリ性でもない)中性の / (電気が)中性の,(物体が)帯電していない / (自動車などのギアが)ニュートラルの / (文法で)中性の / 〈C〉(戦争・論争などで)中立の人;中立国民;中立国 / 〈C〉くすんだ色,灰色 / 〈U〉(自動車などのギヤの)ニュートラル(動力のかかっていない状態・位置)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/07/22 22:04:27」(JST)

wiki en

[Wiki en表示]

Neprilysin, also known as membrane metallo-endopeptidase (MME), neutral endopeptidase (NEP), cluster of differentiation 10 (CD10), and common acute lymphoblastic leukemia antigen (CALLA) is an enzyme that in humans is encoded by the MME gene. Neprilysin is a zinc-dependent metalloprotease that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones including glucagon, enkephalins, substance P, neurotensin, oxytocin, and bradykinin.^[1] It also degrades the amyloid beta peptide whose abnormal misfolding and aggregation in neural tissue has been implicated as a cause of Alzheimer's disease. Synthesized as a membrane-bound protein, the neprilysin ectodomain is released into the extracellular domain after it has been transported from the Golgi apparatus to the cell surface.

Neprilysin is expressed in a wide variety of tissues and is particularly abundant in kidney. It is also a common acute lymphocytic leukemia antigen that is an important cell surface marker in the diagnosis of human acute lymphocytic leukemia (ALL). This protein is present on leukemic cells of pre-B phenotype, which represent 85% of cases of ALL.^[1]

Hematopoetic Progenitors expressing CD10 are considered "Common Lymphoid Progenitors," which means they can differentiate into T, B or Natural Killer cells.^[2] CD10 is of use in hematological diagnosis since it is expressed by early B, pro-B and pre-B lymphocytes, and by lymph node germinal centers.^[3] Hematologic diseases in which it is positive include ALL, angioimmunoblastic T cell lymphoma, Burkitt lymphoma, CML in blast crisis (90%), diffuse large B-cell lymphoma (variable), follicular center cells (70%), hairy cell leukemia (10%), and myeloma (some). It tends to be negative in AML, CLL, mantle cell lymphoma, and marginal zone lymphoma. CD10 is found on non-T ALL cells, which derive from pre-B lymphocytes, and in germinal center-related non-Hodgkin lymphoma such as Burkitt lymphoma and follicular lymphoma, but not on leukemia cells or lymphomas, which originate in more mature B cells.^[4]

Amyloid beta regulation

Neprilysin-deficient knockout mice show both Alzheimer's-like behavioral impairment and amyloid-beta deposition in the brain,^[5] providing strong evidence for the protein's association with the Alzheimer's disease process. Because neprilysin is thought to be the rate-limiting step in amyloid beta degradation,^[6] it has been considered a potential therapeutic target; compounds such as the peptide hormone somatostatin have been identified that increase the enzyme's activity level.^[7] One hypothesis for the strong dependence of Alzheimer's incidence on age focuses on the declining production of somatostatin in the brains of elderly people, which thus depresses the activity of neprilysin and promotes aggregation of unprocessed amyloid beta.^[8] Declining neprilysin activity with increasing age may also be explained by oxidative damage, known to be a causative factor in Alzheimer's disease; higher levels of inappropriately oxidized neprilysin have been found in Alzheimer's patients compared to cognitively normal elderly people.^[9]

Signaling peptides

Neprilysin immunohistochemical staining of normal kidney.

Neprilysin is also associated with other biochemical processes, and is particularly highly expressed in kidney and lung tissues. Inhibitors have been designed with the aim of developing analgesic and antihypertensive agents that act by preventing neprilysin's activity against signaling peptides such as enkephalins, substance P, endothelin, and atrial natriuretic factor.^[10]^[11]

Associations have been observed between neprilysin expression and various types of cancer; however, the relationship between neprilysin expression and carcinogenesis remains obscure. In cancer biomarker studies, the neprilysin gene is often referred to as CD10 or CALLA. In some types of cancer, such as metastatic carcinoma and some advanced melanomas, neprilysin is overexpressed;^[12] in other types, most notably lung cancers, neprilysin is downregulated, and thus unable to modulate the pro-growth autocrine signaling of cancer cells via secreted peptides such as mammalian homologs related to bombesin.^[13] Some plant extracts (methanol extracts of Ceropegia rupicola, Kniphofia sumarae, Plectranthus cf barbatus, and an aqueous extract of Pavetta longiflora) were found able to inhibit the enzymatic activity of neutral endopeptidase.^[14]

Inhibitors

AHU-377, a component of LCZ696
Omapatrilat
RB-101
UK-414,495

Immunochemistry

CD10 is used in clinical pathology for diagnostic purpose.

In lymphomas and leukemias

Acute lymphoblastic leukemia (ALL) cells are CD10⁺.
Follicular lymphoma (follicle centre cell lymphoma) are CD10⁺.
Burkitt Lymphoma cells are CD10⁺.
CD10⁺ diffuse large B cell lymphoma (CD10⁺ DLBLC)^[15]
- Marker for germinal center phenotype (CD10, HGAL, BCL6, CD38) are considered a favorable prognostic factor,^[16]^[17] but CD10⁺, BCL2⁺ tumors could have poorer survival.^[18] For some authors, CD10 expression in DLBCL does not influence survival.^[19]
Angioimmunoblastic T cell lymphoma (AITL) are CD10⁺^[20]^[21] and distinguishes AITL from other T cell lymphomas (CD10^–)^[22]
- Some benign T cells can be CD10⁺^[23]

In epithelial tumors

Clear cell renal cell carcinoma (Clear cell RCC)
- CD10⁺ distinguishes renal cell carcinoma, conventional type with eosinophilic morphology from its mimickers. Chromophobe carcinoma and oncocytoma are CD10^-.^[24]

Pancreatic tumors
- Solid pseudopapillary tumours are CD10⁺.^[25]
- CD10⁺ differentiates mucinous cystic neoplasms (CD10⁺/CK20+) from intraductal papillary mucinous neoplasm of branch duct type (CD10^–/CK20-).^[25]

Cutaneous tumors
- CD10 may differentiate basal cell carcinoma (CD10 epithelial staining) from trichoblastoma (CD10 peritumoral stromal staining), basal cell carcinoma with follicular differentiation (CD10 stromal and epithelial staining)^[26] and squamous cell carcinoma (strong stromal staining).^[27]
- CD10 differentiates CD10⁺ atypical fibroxanthoma from CD10^– spindle cell melanoma and sarcomatoid squamous cell carcinoma.

Urothelial tumors express CD10 (42-67%).^[28]
- CD10 expression is strongly correlated with high tumor grade and stage in urothelial carcinoma of the bladder. CD10 may be associated with tumor progression in bladder cancer pathogenesis.^[29]

In other tumors

CD10 expression might be one of the characteristics of müllerian system-derived neoplastic mesenchymal cells.^[30]
- Normal endometrial stroma^[31]
- Endometrial stromal sarcoma (ESS) are CD10⁺ (Smooth muscle tumors are usually CD10^–,^[32] but can be CD10⁺ ^[30]
- Malignant müllerian mixed tumor (MMMT)
- Müllerian adenosarcoma
- Uterine high-grade leiomyosarcoma
- Uterine rhabdomyosarcoma

Vascular tumors
- Epithelioid hemangioendothelioma are mostly CD10⁺.^[33]
- Hemangioblastoma is usually CD10^– (metastatic renal cell carcinoma is CD10⁺)^[34]^[35]

References

^ ^a ^b "Entrez Gene: Membrane metallo-endopeptidase".
^ Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset. http://www.ncbi.nlm.nih.gov/pubmed/7584137
^ Singh C (2011-02-25). "CD10". CD Markers. PathologyOutlines.com, Inc.
^ Papandreou CN, Nanus DM (January 2010). "Is methylation the key to CD10 loss?". J. Pediatr. Hematol. Oncol. 32 (1): 2–3. doi:10.1097/MPH.0b013e3181c74aca. PMID 20051779.
^ Madani R, Poirier R, Wolfer DP, Welzl H, Groscurth P, Lipp HP, Lu B, El Mouedden M, Mercken M, Nitsch RM, Mohajeri MH (December 2006). "Lack of neprilysin suffices to generate murine amyloid-like deposits in the brain and behavioral deficit in vivo". J. Neurosci. Res. 84 (8): 1871–8. doi:10.1002/jnr.21074. PMID 16998901.
^ Iwata N, Tsubuki S, Takaki Y, Watanabe K, Sekiguchi M, Hosoki E, Kawashima-Morishima M, Lee HJ, Hama E, Sekine-Aizawa Y, Saido TC (February 2000). "Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition". Nat. Med. 6 (2): 143–50. doi:10.1038/72237. PMID 10655101.
^ Iwata N, Higuchi M, Saido TC (November 2005). "Metabolism of amyloid-beta peptide and Alzheimer's disease". Pharmacol. Ther. 108 (2): 129–48. doi:10.1016/j.pharmthera.2005.03.010. PMID 16112736.
^ Hama E, Saido TC (2005). "Etiology of sporadic Alzheimer's disease: somatostatin, neprilysin, and amyloid beta peptide". Med. Hypotheses 65 (3): 498–500. doi:10.1016/j.mehy.2005.02.045. PMID 15921860.
^ Wang DS, Iwata N, Hama E, Saido TC, Dickson DW (October 2003). "Oxidized neprilysin in aging and Alzheimer's disease brains". Biochem. Biophys. Res. Commun. 310 (1): 236–41. doi:10.1016/j.bbrc.2003.09.003. PMID 14511676.
^ Sahli S, Stump B, Welti T, Schweizer WB, Diederich R, Blum-Kaelin D, Aebi JD, Böhm H-J (April 2005). "A New Class of Inhibitors for the Metalloprotease Neprilysin Based on a Central Imidazole Scaffold". Helvetica Chimica Acta 88 (4): 707–730. doi:10.1002/hlca.200590050.
^ Oefner C, Roques BP, Fournie-Zaluski MC, Dale GE (February 2004). "Structural analysis of neprilysin with various specific and potent inhibitors". Acta Crystallogr. D Biol. Crystallogr. 60 (Pt 2): 392–6. doi:10.1107/S0907444903027410. PMID 14747736.
^ Velazquez EF, Yancovitz M, Pavlick A, Berman R, Shapiro R, Bogunovic D, O'Neill D, Yu YL, Spira J, Christos PJ, Zhou XK, Mazumdar M, Nanus DM, Liebes L, Bhardwaj N, Polsky D, Osman I (2007). "Clinical relevance of neutral endopeptidase (NEP/CD10) in melanoma". J Transl Med 5: 2. doi:10.1186/1479-5876-5-2. PMC 1770905. PMID 17207277.
^ Cohen AJ, Bunn PA, Franklin W, Magill-Solc C, Hartmann C, Helfrich B, Gilman L, Folkvord J, Helm K, Miller YE (February 1996). "Neutral endopeptidase: variable expression in human lung, inactivation in lung cancer, and modulation of peptide-induced calcium flux". Cancer Res. 56 (4): 831–9. PMID 8631021.
^ Alasbahi R, Melzig MF (January 2008). "Screening of some Yemeni medicinal plants for inhibitory activity against peptidases". Pharmazie 63 (1): 86–8. PMID 18271311.
^ McGowan P, Nelles N, Wimmer J, Williams D, Wen J, Li M, Ewton A, Curry C, Zu Y, Sheehan A, Chang CC (2012). "Differentiating between Burkitt lymphoma and CD10+ diffuse large B-cell lymphoma: the role of commonly used flow cytometry cell markers and the application of a multiparameter scoring system". Am. J. Clin. Pathol. 137 (4): 665–70. doi:10.1309/AJCP3FEPX5BEEKGX. PMID 22431545.
^ Berglund M, Thunberg U, Amini RM, Book M, Roos G, Erlanson M, Linderoth J, Dictor M, Jerkeman M, Cavallin-Ståhl E, Sundström C, Rehn-Eriksson S, Backlin C, Hagberg H, Rosenquist R, Enblad G (2005). "Evaluation of immunophenotype in diffuse large B-cell lymphoma and its impact on prognosis". Mod. Pathol. 18 (8): 1113–20. doi:10.1038/modpathol.3800396. PMID 15920553.
^ Höller S, Horn H, Lohr A, Mäder U, Katzenberger T, Kalla J, Bernd HW, Went P, Ott MM, Müller-Hermelink HK, Rosenwald A, Ott G (2009). "A cytomorphological and immunohistochemical profile of aggressive B-cell lymphoma: high clinical impact of a cumulative immunohistochemical outcome predictor score". J Hematop 2 (4): 187–94. doi:10.1007/s12308-009-0044-x. PMC 2798934. PMID 20309427.
^ Xu Y, McKenna RW, Molberg KH, Kroft SH (2001). "Clinicopathologic analysis of CD10+ and CD10- diffuse large B-cell lymphoma. Identification of a high-risk subset with coexpression of CD10 and bcl-2". Am. J. Clin. Pathol. 116 (2): 183–90. doi:10.1309/J7RN-UXAY-55GX-BUNK. PMID 11488064.
^ Fabiani B, Delmer A, Lepage E, Guettier C, Petrella T, Brière J, Penny AM, Copin MC, Diebold J, Reyes F, Gaulard P, Molina TJ (2004). "CD10 expression in diffuse large B-cell lymphomas does not influence survival". Virchows Arch. 445 (6): 545–51. doi:10.1007/s00428-004-1129-7. PMID 15517363.
^ Baseggio L, Traverse-Glehen A, Berger F, Ffrench M, Jallades L, Morel D, Goedert G, Magaud JP, Salles G, Felman P (2011). "CD10 and ICOS expression by multiparametric flow cytometry in angioimmunoblastic T-cell lymphoma". Mod. Pathol. 24 (7): 993–1003. doi:10.1038/modpathol.2011.53. PMID 21499231.
^ Yuan CM, Vergilio JA, Zhao XF, Smith TK, Harris NL, Bagg A (2005). "CD10 and BCL6 expression in the diagnosis of angioimmunoblastic T-cell lymphoma: utility of detecting CD10+ T cells by flow cytometry". Hum. Pathol. 36 (7): 784–91. doi:10.1016/j.humpath.2005.05.008. PMID 16084948.
^ Attygalle AD, Diss TC, Munson P, Isaacson PG, Du MQ, Dogan A (2004). "CD10 expression in extranodal dissemination of angioimmunoblastic T-cell lymphoma". Am. J. Surg. Pathol. 28 (1): 54–61. doi:10.1097/00000478-200401000-00005. PMID 14707864.
^ Cook JR, Craig FE, Swerdlow SH (2003). "Benign CD10-positive T cells in reactive lymphoid proliferations and B-cell lymphomas". Mod. Pathol. 16 (9): 879–85. doi:10.1097/01.MP.0000084630.64243.D1. PMID 13679451.
^ Yasir S, Herrera L, Gomez-Fernandez C, Reis IM, Umar S, Leveillee R, Kava B, Jorda M (2012). "CD10⁺ and CK7/RON- immunophenotype distinguishes renal cell carcinoma, conventional type with eosinophilic morphology from its mimickers". Appl. Immunohistochem. Mol. Morphol. 20 (5): 454–61. doi:10.1097/PAI.0b013e31823fecd3. PMID 22417859.
^ ^a ^b Notohara K, Hamazaki S, Tsukayama C, Nakamoto S, Kawabata K, Mizobuchi K, Sakamoto K, Okada S (2000). "Solid-pseudopapillary tumor of the pancreas: immunohistochemical localization of neuroendocrine markers and CD10". Am. J. Surg. Pathol. 24 (10): 1361–71. doi:10.1097/00000478-200010000-00005. PMID 11023097.
^ Córdoba A, Guerrero D, Larrinaga B, Iglesias ME, Arrechea MA, Yanguas JI (2009). "Bcl-2 and CD10 expression in the differential diagnosis of trichoblastoma, basal cell carcinoma, and basal cell carcinoma with follicular differentiation". Int. J. Dermatol. 48 (7): 713–7. doi:10.1111/j.1365-4632.2009.04076.x. PMID 19570076.
^ Sari Aslani F, Akbarzadeh-Jahromi M, Jowkar F (2013). "Value of CD10 Expression in Differentiating Cutaneous Basal from Squamous Cell Carcinomas and Basal Cell Carcinoma from Trichoepithelioma". Iran J Med Sci 38 (2): 100–6. PMC 3700055. PMID 23825889.
^ Murali R, Delprado W (2005). "CD10 immunohistochemical staining in urothelial neoplasms". Am. J. Clin. Pathol. 124 (3): 371–9. doi:10.1309/04BH-F6A8-0BQM-H7HT. PMID 16191505.
^ Bahadir B, Behzatoglu K, Bektas S, Bozkurt ER, Ozdamar SO (2009). "CD10 expression in urothelial carcinoma of the bladder". Diagn Pathol 4: 38. doi:10.1186/1746-1596-4-38. PMC 2780995. PMID 19917108.
^ ^a ^b Mikami Y, Hata S, Kiyokawa T, Manabe T (2002). "Expression of CD10 in malignant müllerian mixed tumors and adenosarcomas: an immunohistochemical study". Mod. Pathol. 15 (9): 923–30. doi:10.1097/01.MP.0000026058.33869.DB. PMID 12218209.
^ McCluggage WG, Sumathi VP, Maxwell P (2001). "CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms". Histopathology 39 (3): 273–8. doi:10.1046/j.1365-2559.2001.01215.x. PMID 11532038.
^ Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S (2005). "Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer". J. Clin. Oncol. 23 (16): 3706–12. doi:10.1200/JCO.2005.00.232. PMID 15867200.
^ Weinreb I, Cunningham KS, Perez-Ordoñez B, Hwang DM (2009). "CD10 is expressed in most epithelioid hemangioendotheliomas: a potential diagnostic pitfall". Arch. Pathol. Lab. Med. 133 (12): 1965–8. doi:10.1043/1543-2165-133.12.1965. PMID 19961253.
^ Jung SM, Kuo TT (2005). "Immunoreactivity of CD10 and inhibin alpha in differentiating hemangioblastoma of central nervous system from metastatic clear cell renal cell carcinoma". Mod. Pathol. 18 (6): 788–94. doi:10.1038/modpathol.3800351. PMID 15578072.
^ Yin WH, Li J, Chan JK (2012). "Sporadic haemangioblastoma of the kidney with rhabdoid features and focal CD10 expression: report of a case and literature review". Diagn Pathol 7: 39. doi:10.1186/1746-1596-7-39. PMC 3364142. PMID 22497861.

External links

The MEROPS online database for peptidases and their inhibitors: M13.001
Neprilysin at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. ACE 阻害薬誘発性血管浮腫 ace inhibitor induced angioedema
2. 膜性腎症の原因および診断 causes and diagnosis of membranous nephropathy
3. 先天性乳児ネフローゼ症候群 congenital and infantile nephrotic syndrome
4. 心不全におけるエンドセリンの役割 role of endothelin in heart failure
5. 心不全に対する試験中および新規の治療 investigational and emerging therapies for heart failure

English Journal

Neutral endopeptidase and natriuretic peptide receptors participate in the regulation of C-type natriuretic peptide expression in renal interstitial fibrosis.

Hu P1, Xia X1, Xuan Q2, Huang BY1, Liu SY1, Zhang DD1, Jiang GM1, Xu Y1, Qin YH3.
Journal of receptor and signal transduction research.J Recept Signal Transduct Res.2017 Feb;37(1):71-83. doi: 10.3109/10799893.2016.1155068. Epub 2016 Jun 8.
The initiation and progression of renal interstitial fibrosis (RIF) is a complicated process in which many factors may play an activate role. Among these factors, C-type natriuretic peptide (CNP) is an endothelium-derived hormone and acts in a local, paracrine fashion to regulate vascular smooth mus
PMID 27278005

The safety of sacubitril-valsartan for the treatment of chronic heart failure.

Tyler JM1, Teerlink JR1,2.
Expert opinion on drug safety.Expert Opin Drug Saf.2017 Jan 6. doi: 10.1080/14740338.2017.1279144. [Epub ahead of print]
INTRODUCTION: Sacubitril-valsartan is a combination drug that contains the neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan. In 2015, the US Food and Drug Administration approved sacubitril-valsartan for treatment of heart failure patients with reduced ejection fraction
PMID 28060547

Mature CD10+ and immature CD10- neutrophils present in G-CSF-treated donors display opposite effects on T cells.

Marini O1, Costa S1, Bevilacqua D1, Calzetti F1, Tamassia N1, Spina C2, De Sabata D2, Tinazzi E3, Lunardi C3, Scupoli MT4, Cavallini C4, Zoratti E5, Tinazzi I6, Marchetta A6, Vassanelli A7, Cantini M7, Gandini G7, Ruzzenente A8, Guglielmi A8, Missale F9, Vermi W9, Tecchio C2, Cassatella MA1, Scapini P10.
Blood.Blood.2017 Jan 4. pii: blood-2016-04-713206. doi: 10.1182/blood-2016-04-713206. [Epub ahead of print]
The identification of discrete neutrophil populations, as well as the characterization of their immunoregulatory properties, is an emerging topic under extensive investigation. In such regard, the presence of circulating CD66b+-neutrophil populations, exerting either immunosuppressive or proinflamma
PMID 28053192

Japanese Journal

Physiological Relevance of Hydrolysis of Atrial Natriuretic Peptide by Endothelin-Converting Enzyme-1

Nakayama Kazuhiko,Emoto Noriaki,Suzuki Yoko,Vignon-Zellweger Nicolas,Yagi Keiko,Hirata Ken-Ichi
The Kobe journal of the medical sciences 58(1), 12-18, 2012
… ANP was shown to be hydrolyzed by neutral endopeptidase 24.11 (NEP) which shares important structural features with ECE-1. …
NAID 110009591545

Generation of Target-Selective Drug Candidate Structures Using Molecular Evolutionary Algorithm with SVM Classifiers

KAWAI Kentaro,YOSHIMARU Kazutaka,TAKAHASHI Yoshimasa
Journal of computer chemistry, Japan 10(1), 79-87, 2011-12-31
… We performed molecular evolutionary computation using the SVM classifiers in order to generate candidate chemical structures for antihypertensive drugs of two different therapeutic classes of angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP). …
NAID 10031135595

Y-13 子宮内膜症間質細胞においてNeutral endopeptidaseはプロゲステロンにより誘導され,細胞骨格-CD44結合を阻害し,細胞外マトリックスであるヒアルロン酸への接着を阻害する(生殖,優秀演題賞候補プログラム,第63回日本産科婦人科学会学術講演会)

岩瀬明,後藤真紀,眞鍋修一,中村智子,廣川和加奈,中原辰夫,小林浩治,滝川幸子,吉川史隆
日本産科婦人科學會雜誌 63(2), 706, 2011-02-01
NAID 110008509540

「enkephalinase」

Membrane metallo-endopeptidase
	; The structure of the neprilysin ectodomain in complex with a zinc-chelating inhibitor. The zinc atom is shown as a gray sphere and the inhibitor is shown in green. Rendering based on 1r1h.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1DMT, 1R1H, 1R1I, 1R1J, 1Y8J, 2QPJ, 2YB9
Identifiers
Symbols	MME ; CALLA; CD10; NEP; SFE
External IDs	OMIM: 120520 MGI: 97004 HomoloGene: 5275 ChEMBL: 1944 GeneCards: MME Gene
EC number	3.4.24.11
Gene ontology
Molecular function	• endopeptidase activity; • metalloendopeptidase activity; • protein binding; • zinc ion binding; • peptide binding;
Cellular component	• cytoplasm; • plasma membrane; • integral to plasma membrane; • brush border; • synaptic vesicle; • integral to membrane; • axon; • dendrite; • neuron projection terminus; • synapse;
Biological process	• kidney development; • angiotensin maturation; • proteolysis; • peptide metabolic process; • sensory perception of pain; • cellular protein metabolic process; • creatinine metabolic process; • beta-amyloid metabolic process; • cellular response to cytokine stimulus; • cellular response to UV-A; • cellular response to UV-B; • replicative senescence;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

エンケファリナーゼ、エンケファリン分解酵素

関: neprilysin、neutral endopeptidase

「中性エンドペプチダーゼ」

　　[★]

英: neutral endopeptidase
関: エンケファリナーゼ、ネプリライシン

「neprilysin」

　　[★]

ネプリライシン

関: enkephalinase、neutral endopeptidase

同: CDl'O

「NEP」

　　[★]

同: neutral endopeptidase

「PHEX phosphate regulating neutral endopeptidase」

　　[★]

PHEXリン酸調節中性エンドペプチダーゼ

「neutral」

　　[★]

adj.

中性の、中立の

[entrez-1] "Entrez Gene: Membrane metallo-endopeptidase".

[2] Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset. http://www.ncbi.nlm.nih.gov/pubmed/7584137

[urlCD_Markers_-_CD10-3] Singh C (2011-02-25). "CD10". CD Markers. PathologyOutlines.com, Inc.

[pmid20051779-4] Papandreou CN, Nanus DM (January 2010). "Is methylation the key to CD10 loss?". J. Pediatr. Hematol. Oncol. 32 (1): 2–3. doi:10.1097/MPH.0b013e3181c74aca. PMID 20051779.

[Madani-5] Madani R, Poirier R, Wolfer DP, Welzl H, Groscurth P, Lipp HP, Lu B, El Mouedden M, Mercken M, Nitsch RM, Mohajeri MH (December 2006). "Lack of neprilysin suffices to generate murine amyloid-like deposits in the brain and behavioral deficit in vivo". J. Neurosci. Res. 84 (8): 1871–8. doi:10.1002/jnr.21074. PMID 16998901.

[Iwata1-6] Iwata N, Tsubuki S, Takaki Y, Watanabe K, Sekiguchi M, Hosoki E, Kawashima-Morishima M, Lee HJ, Hama E, Sekine-Aizawa Y, Saido TC (February 2000). "Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition". Nat. Med. 6 (2): 143–50. doi:10.1038/72237. PMID 10655101.

[Iwata-7] Iwata N, Higuchi M, Saido TC (November 2005). "Metabolism of amyloid-beta peptide and Alzheimer's disease". Pharmacol. Ther. 108 (2): 129–48. doi:10.1016/j.pharmthera.2005.03.010. PMID 16112736.

[Hama-8] Hama E, Saido TC (2005). "Etiology of sporadic Alzheimer's disease: somatostatin, neprilysin, and amyloid beta peptide". Med. Hypotheses 65 (3): 498–500. doi:10.1016/j.mehy.2005.02.045. PMID 15921860.

[Wang-9] Wang DS, Iwata N, Hama E, Saido TC, Dickson DW (October 2003). "Oxidized neprilysin in aging and Alzheimer's disease brains". Biochem. Biophys. Res. Commun. 310 (1): 236–41. doi:10.1016/j.bbrc.2003.09.003. PMID 14511676.

[Sahli-10] Sahli S, Stump B, Welti T, Schweizer WB, Diederich R, Blum-Kaelin D, Aebi JD, Böhm H-J (April 2005). "A New Class of Inhibitors for the Metalloprotease Neprilysin Based on a Central Imidazole Scaffold". Helvetica Chimica Acta 88 (4): 707–730. doi:10.1002/hlca.200590050.

[Oefner-11] Oefner C, Roques BP, Fournie-Zaluski MC, Dale GE (February 2004). "Structural analysis of neprilysin with various specific and potent inhibitors". Acta Crystallogr. D Biol. Crystallogr. 60 (Pt 2): 392–6. doi:10.1107/S0907444903027410. PMID 14747736.

[Velazquez-12] Velazquez EF, Yancovitz M, Pavlick A, Berman R, Shapiro R, Bogunovic D, O'Neill D, Yu YL, Spira J, Christos PJ, Zhou XK, Mazumdar M, Nanus DM, Liebes L, Bhardwaj N, Polsky D, Osman I (2007). "Clinical relevance of neutral endopeptidase (NEP/CD10) in melanoma". J Transl Med 5: 2. doi:10.1186/1479-5876-5-2. PMC 1770905. PMID 17207277.

[Cohen-13] Cohen AJ, Bunn PA, Franklin W, Magill-Solc C, Hartmann C, Helfrich B, Gilman L, Folkvord J, Helm K, Miller YE (February 1996). "Neutral endopeptidase: variable expression in human lung, inactivation in lung cancer, and modulation of peptide-induced calcium flux". Cancer Res. 56 (4): 831–9. PMID 8631021.

[pmid18271311-14] Alasbahi R, Melzig MF (January 2008). "Screening of some Yemeni medicinal plants for inhibitory activity against peptidases". Pharmazie 63 (1): 86–8. PMID 18271311.

[pmid22431545-15] McGowan P, Nelles N, Wimmer J, Williams D, Wen J, Li M, Ewton A, Curry C, Zu Y, Sheehan A, Chang CC (2012). "Differentiating between Burkitt lymphoma and CD10+ diffuse large B-cell lymphoma: the role of commonly used flow cytometry cell markers and the application of a multiparameter scoring system". Am. J. Clin. Pathol. 137 (4): 665–70. doi:10.1309/AJCP3FEPX5BEEKGX. PMID 22431545.

[pmid15920553-16] Berglund M, Thunberg U, Amini RM, Book M, Roos G, Erlanson M, Linderoth J, Dictor M, Jerkeman M, Cavallin-Ståhl E, Sundström C, Rehn-Eriksson S, Backlin C, Hagberg H, Rosenquist R, Enblad G (2005). "Evaluation of immunophenotype in diffuse large B-cell lymphoma and its impact on prognosis". Mod. Pathol. 18 (8): 1113–20. doi:10.1038/modpathol.3800396. PMID 15920553.

[pmid20309427-17] Höller S, Horn H, Lohr A, Mäder U, Katzenberger T, Kalla J, Bernd HW, Went P, Ott MM, Müller-Hermelink HK, Rosenwald A, Ott G (2009). "A cytomorphological and immunohistochemical profile of aggressive B-cell lymphoma: high clinical impact of a cumulative immunohistochemical outcome predictor score". J Hematop 2 (4): 187–94. doi:10.1007/s12308-009-0044-x. PMC 2798934. PMID 20309427.

[pmid11488064-18] Xu Y, McKenna RW, Molberg KH, Kroft SH (2001). "Clinicopathologic analysis of CD10+ and CD10- diffuse large B-cell lymphoma. Identification of a high-risk subset with coexpression of CD10 and bcl-2". Am. J. Clin. Pathol. 116 (2): 183–90. doi:10.1309/J7RN-UXAY-55GX-BUNK. PMID 11488064.

[pmid15517363-19] Fabiani B, Delmer A, Lepage E, Guettier C, Petrella T, Brière J, Penny AM, Copin MC, Diebold J, Reyes F, Gaulard P, Molina TJ (2004). "CD10 expression in diffuse large B-cell lymphomas does not influence survival". Virchows Arch. 445 (6): 545–51. doi:10.1007/s00428-004-1129-7. PMID 15517363.

[pmid21499231-20] Baseggio L, Traverse-Glehen A, Berger F, Ffrench M, Jallades L, Morel D, Goedert G, Magaud JP, Salles G, Felman P (2011). "CD10 and ICOS expression by multiparametric flow cytometry in angioimmunoblastic T-cell lymphoma". Mod. Pathol. 24 (7): 993–1003. doi:10.1038/modpathol.2011.53. PMID 21499231.

[pmid16084948-21] Yuan CM, Vergilio JA, Zhao XF, Smith TK, Harris NL, Bagg A (2005). "CD10 and BCL6 expression in the diagnosis of angioimmunoblastic T-cell lymphoma: utility of detecting CD10+ T cells by flow cytometry". Hum. Pathol. 36 (7): 784–91. doi:10.1016/j.humpath.2005.05.008. PMID 16084948.

[pmid14707864-22] Attygalle AD, Diss TC, Munson P, Isaacson PG, Du MQ, Dogan A (2004). "CD10 expression in extranodal dissemination of angioimmunoblastic T-cell lymphoma". Am. J. Surg. Pathol. 28 (1): 54–61. doi:10.1097/00000478-200401000-00005. PMID 14707864.

[pmid13679451-23] Cook JR, Craig FE, Swerdlow SH (2003). "Benign CD10-positive T cells in reactive lymphoid proliferations and B-cell lymphomas". Mod. Pathol. 16 (9): 879–85. doi:10.1097/01.MP.0000084630.64243.D1. PMID 13679451.

[pmid22417859-24] Yasir S, Herrera L, Gomez-Fernandez C, Reis IM, Umar S, Leveillee R, Kava B, Jorda M (2012). "CD10⁺ and CK7/RON- immunophenotype distinguishes renal cell carcinoma, conventional type with eosinophilic morphology from its mimickers". Appl. Immunohistochem. Mol. Morphol. 20 (5): 454–61. doi:10.1097/PAI.0b013e31823fecd3. PMID 22417859.

[pmid11023097-25] Notohara K, Hamazaki S, Tsukayama C, Nakamoto S, Kawabata K, Mizobuchi K, Sakamoto K, Okada S (2000). "Solid-pseudopapillary tumor of the pancreas: immunohistochemical localization of neuroendocrine markers and CD10". Am. J. Surg. Pathol. 24 (10): 1361–71. doi:10.1097/00000478-200010000-00005. PMID 11023097.

[pmid19570076-26] Córdoba A, Guerrero D, Larrinaga B, Iglesias ME, Arrechea MA, Yanguas JI (2009). "Bcl-2 and CD10 expression in the differential diagnosis of trichoblastoma, basal cell carcinoma, and basal cell carcinoma with follicular differentiation". Int. J. Dermatol. 48 (7): 713–7. doi:10.1111/j.1365-4632.2009.04076.x. PMID 19570076.

[pmid23825889-27] Sari Aslani F, Akbarzadeh-Jahromi M, Jowkar F (2013). "Value of CD10 Expression in Differentiating Cutaneous Basal from Squamous Cell Carcinomas and Basal Cell Carcinoma from Trichoepithelioma". Iran J Med Sci 38 (2): 100–6. PMC 3700055. PMID 23825889.

[pmid16191505-28] Murali R, Delprado W (2005). "CD10 immunohistochemical staining in urothelial neoplasms". Am. J. Clin. Pathol. 124 (3): 371–9. doi:10.1309/04BH-F6A8-0BQM-H7HT. PMID 16191505.

[pmid19917108-29] Bahadir B, Behzatoglu K, Bektas S, Bozkurt ER, Ozdamar SO (2009). "CD10 expression in urothelial carcinoma of the bladder". Diagn Pathol 4: 38. doi:10.1186/1746-1596-4-38. PMC 2780995. PMID 19917108.

[pmid12218209-30] Mikami Y, Hata S, Kiyokawa T, Manabe T (2002). "Expression of CD10 in malignant müllerian mixed tumors and adenosarcomas: an immunohistochemical study". Mod. Pathol. 15 (9): 923–30. doi:10.1097/01.MP.0000026058.33869.DB. PMID 12218209.

[pmid11532038-31] McCluggage WG, Sumathi VP, Maxwell P (2001). "CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms". Histopathology 39 (3): 273–8. doi:10.1046/j.1365-2559.2001.01215.x. PMID 11532038.

[pmid15867200-32] Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S (2005). "Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer". J. Clin. Oncol. 23 (16): 3706–12. doi:10.1200/JCO.2005.00.232. PMID 15867200.

[pmid19961253-33] Weinreb I, Cunningham KS, Perez-Ordoñez B, Hwang DM (2009). "CD10 is expressed in most epithelioid hemangioendotheliomas: a potential diagnostic pitfall". Arch. Pathol. Lab. Med. 133 (12): 1965–8. doi:10.1043/1543-2165-133.12.1965. PMID 19961253.

[pmid15578072-34] Jung SM, Kuo TT (2005). "Immunoreactivity of CD10 and inhibin alpha in differentiating hemangioblastoma of central nervous system from metastatic clear cell renal cell carcinoma". Mod. Pathol. 18 (6): 788–94. doi:10.1038/modpathol.3800351. PMID 15578072.

[pmid22497861-35] Yin WH, Li J, Chan JK (2012). "Sporadic haemangioblastoma of the kidney with rhabdoid features and focal CD10 expression: report of a case and literature review". Diagn Pathol 7: 39. doi:10.1186/1746-1596-7-39. PMC 3364142. PMID 22497861.

リンク元	「enkephalinase」「中性エンドペプチダーゼ」「neprilysin」「NEP」
拡張検索	「PHEX phosphate regulating neutral endopeptidase」
関連記事	「neutral」

匿名

検索

案内

案内

neutral endopeptidase