Neprilysin
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| Location (UCSC) | Chr 3: 155.02 – 155.18 Mb | Chr 3: 63.15 – 63.29 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Neprilysin (
Neprilysin is expressed in a wide variety of tissues and is particularly abundant in kidney. It is also a common
Hematopoietic progenitors expressing CD10 are considered "common lymphoid progenitors", which means they can differentiate into T, B or natural killer cells.
Amyloid beta regulation
Neprilysin-deficient
Signaling peptides
Neprilysin is also associated with other biochemical processes, and is particularly highly expressed in
Associations have been observed between neprilysin expression and various types of
Inhibitors
Inhibitors have been designed with the aim of developing
Some are intended to treat heart failure.[18]
- Sacubitril/valsartan (Entresto/LCZ696), which has been tested against enalapril in patients with heart failure.[18]
- Sacubitril (AHU-377), a prodrug which is a component of sacubitril/valsartan
- Sacubitrilat (LBQ657), the active form of sacubitril
- RB-101, an enkephalinase inhibitor, used in scientific research.
- UK-414,495
- Omapatrilat (dual inhibitor of NEP and angiotensin-converting enzyme) developed by BMS did not receive FDA approval due to angioedema safety concerns.
- Ecadotril
- Candoxatril
Other dual inhibitors of NEP with ACE/angiotensin receptor were (in 2003) being developed by pharmaceutical companies.[19]
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+ DLBCL)[20]
- Marker for germinal center phenotype (CD10, HGAL, BCL6, CD38) are considered a favorable prognostic factor,
- Angioimmunoblastic T cell lymphoma (AITL) are CD10+[25][26] and distinguishes AITL from other T cell lymphomas (CD10−)[27]
- Some benign T cells can be CD10+[28]
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−.[29]
- Pancreatic tumors
- Solid pseudopapillary tumours are CD10+.[30]
- CD10+ differentiates mucinous cystic neoplasms (CD10+/CK20+) from intraductal papillary mucinous neoplasm of branch duct type (CD10−/CK20-).[30]
- Cutaneous tumors
- CD10 may differentiate squamous cell carcinoma (strong stromal staining).[32]
- CD10 differentiates CD10+ squamous cell carcinoma.
- CD10 may differentiate
- Urothelial tumors express CD10 (42-67%).[33]
- 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.[34]
In other tumors
- CD10 expression might be one of the characteristics of müllerian system-derived neoplastic mesenchymal cells.[35]
- Normal endometrial stroma[36]
- Malignant müllerian mixed tumor (MMMT)
- Müllerian adenosarcoma
- Uterine high-grade leiomyosarcoma
- Uterine rhabdomyosarcoma
- Vascular tumors
- Epithelioid hemangioendothelioma are mostly CD10+.[38]
- Hemangioblastoma is usually CD10− (metastatic renal cell carcinoma is CD10+)[39][40]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000196549 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027820 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: Membrane metallo-endopeptidase".
- PMID 7584137.
- ^ Singh C (2011-02-25). "CD10". CD Markers. PathologyOutlines.com, Inc.
- PMID 20051779.
- S2CID 46527377.
- S2CID 22431826.
- PMID 16112736.
- PMID 14511676.
- ^ .
- ^ PMID 14747736.
- PMID 17207277.
- PMID 8631021.
- PMID 18271311.
- ^ S2CID 11383.
- S2CID 85007768.
- PMID 22431545.
- S2CID 7563005.
- PMID 20309427.
- PMID 11488064.
- S2CID 23189608.
- S2CID 22353148.
- PMID 16084948.
- S2CID 25639416.
- S2CID 21020212.
- S2CID 1348915.
- ^ S2CID 3211829.
- S2CID 205395744.
- PMID 23825889.
- PMID 16191505.
- PMID 19917108.
- ^ S2CID 30632093.
- S2CID 42287024.
- PMID 15867200.
- PMID 19961253.
- S2CID 16510470.
- PMID 22497861.
External links
- The MEROPS online database for peptidases and their inhibitors: M13.001
- Neprilysin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: P08473 (Neprilysin) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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![1y8j: Crystal Structure of human NEP complexed with an imidazo[4,5-c]pyridine inhibitor](/File:PDB_1y8j_EBI.jpg)
