neprilysin

Summary

Summary: Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.

Top Publications

  1. pmc In vitro Pb exposure disturbs the balance between Aβ production and elimination: the role of AβPP and neprilysin
    Hui Huang
    Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA
    Neurotoxicology 32:300-6. 2011
  2. pmc Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism
    Gillian I Rice
    Proteolysis Research Group, School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, UK
    Biochem J 383:45-51. 2004
  3. ncbi Metabolic regulation of brain Abeta by neprilysin
    N Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako shi 351 0198 Japan
    Science 292:1550-2. 2001
  4. ncbi Neprilysin degrades both amyloid beta peptides 1-40 and 1-42 most rapidly and efficiently among thiorphan- and phosphoramidon-sensitive endopeptidases
    K Shirotani
    Laboratory for Proteolytic Neuroscience, Brain Science Institute, RIKEN, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    J Biol Chem 276:21895-901. 2001
  5. ncbi Neprilysin gene transfer reduces human amyloid pathology in transgenic mice
    Robert A Marr
    Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    J Neurosci 23:1992-6. 2003
  6. ncbi Neutral endopeptidase protein expression and prognosis in localized prostate cancer
    Iman Osman
    Department of Urology, New York University Cancer Institute, Kaplan Comprehensive Cancer Center, New York, New York, USA
    Clin Cancer Res 10:4096-100. 2004
  7. ncbi Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death
    Malcolm A Leissring
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Harvard Medical School, Boston, MA 02115, USA
    Neuron 40:1087-93. 2003
  8. ncbi Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses
    Efrat Abramov
    Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    Nat Neurosci 12:1567-76. 2009
  9. pmc Neprilysin gene expression requires binding of the amyloid precursor protein intracellular domain to its promoter: implications for Alzheimer disease
    Nikolai D Belyaev
    Faculty of Biological Sciences, Institute of Molecular and Cellular Biology, University of Leeds, Leeds, UK
    EMBO Rep 10:94-100. 2009
  10. ncbi The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function
    A J Turner
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds, UK
    Bioessays 23:261-9. 2001

Research Grants

  1. NEURAL REGULATION OF PANCREATIC FUNCTION
    KIMBERLY SAUNDERS KIRKWOOD; Fiscal Year: 2012
  2. Neprilysin and Pulmonary Vascular Remodeling: Cellular and Molecular Mechanisms
    EDWARD CHARLES DEMPSEY; Fiscal Year: 2013
  3. Insulin Resistance and Vascular Complications in Obesity and Type 2 Diabetes
    Mark A Yorek; Fiscal Year: 2013
  4. Prevention of Diabetic Neuropathy with ACE Inhibitors
    MARK ANTHONY YOREK; Fiscal Year: 2012
  5. Transgenic Mice, Inflammation &the Alzheimer Phenotype
    Marcia N Gordon; Fiscal Year: 2012
  6. Calcitonin for treating X-linked hypophosphatemia
    KARL LEONARD INSOGNA; Fiscal Year: 2012
  7. CHADSS: Chagas Disease Scan Study
    Jamary Oliveira-Filho; Fiscal Year: 2013
  8. Impact of Neprilysin on Islet Function
    Sakeneh Zraika; Fiscal Year: 2013
  9. Somatostatin Agonist Treatment for Cognitive Aging and Dementia
    Ken A Witt; Fiscal Year: 2010
  10. Neprilysin and Peripheral Clearance of Amyloid Peptides
    Louis B Hersh; Fiscal Year: 2010

Detail Information

Publications299 found, 100 shown here

  1. pmc In vitro Pb exposure disturbs the balance between Aβ production and elimination: the role of AβPP and neprilysin
    Hui Huang
    Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA
    Neurotoxicology 32:300-6. 2011
    ..b>Neprilysin (NEP), a rate-limiting catabolic peptidase is involved in Aβ metabolism in vivo...
  2. pmc Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism
    Gillian I Rice
    Proteolysis Research Group, School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, UK
    Biochem J 383:45-51. 2004
    ..cleavage by full-length human ACE, the separate N- and C-domains of ACE, the homologue of ACE, ACE2, and NEP (neprilysin)...
  3. ncbi Metabolic regulation of brain Abeta by neprilysin
    N Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako shi 351 0198 Japan
    Science 292:1550-2. 2001
    ..We examined the role of neprilysin, a candidate Abeta-degrading peptidase, in the metabolism using neprilysin gene-disrupted mice...
  4. ncbi Neprilysin degrades both amyloid beta peptides 1-40 and 1-42 most rapidly and efficiently among thiorphan- and phosphoramidon-sensitive endopeptidases
    K Shirotani
    Laboratory for Proteolytic Neuroscience, Brain Science Institute, RIKEN, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    J Biol Chem 276:21895-901. 2001
    ..1-42-degrading enzyme whose activity is inhibited by thiorphan and phosphoramidon in vivo, we searched for neprilysin (NEP) homologues and cloned neprilysin-like peptidase (NEPLP) alpha, NEPLP beta, and NEPLP gamma cDNAs...
  5. ncbi Neprilysin gene transfer reduces human amyloid pathology in transgenic mice
    Robert A Marr
    Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    J Neurosci 23:1992-6. 2003
    ..b>Neprilysin has recently been implicated as a major extracellular Abeta degrading enzyme in the brain...
  6. ncbi Neutral endopeptidase protein expression and prognosis in localized prostate cancer
    Iman Osman
    Department of Urology, New York University Cancer Institute, Kaplan Comprehensive Cancer Center, New York, New York, USA
    Clin Cancer Res 10:4096-100. 2004
    ..We investigated whether decreased NEP expression in localized prostate cancers is associated with prostate-specific antigen (PSA) relapse after radical prostatectomy...
  7. ncbi Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death
    Malcolm A Leissring
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Harvard Medical School, Boston, MA 02115, USA
    Neuron 40:1087-93. 2003
    ..Here we show that transgenic overexpression of insulin-degrading enzyme (IDE) or neprilysin (NEP) in neurons significantly reduces brain Abeta levels, retards or completely prevents amyloid plaque ..
  8. ncbi Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses
    Efrat Abramov
    Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    Nat Neurosci 12:1567-76. 2009
    ....
  9. pmc Neprilysin gene expression requires binding of the amyloid precursor protein intracellular domain to its promoter: implications for Alzheimer disease
    Nikolai D Belyaev
    Faculty of Biological Sciences, Institute of Molecular and Cellular Biology, University of Leeds, Leeds, UK
    EMBO Rep 10:94-100. 2009
    ..domain of the amyloid precursor protein (AICD) regulates expression of the Abeta-degrading metalloprotease, neprilysin (NEP)...
  10. ncbi The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function
    A J Turner
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds, UK
    Bioessays 23:261-9. 2001
    b>Neprilysin (NEP), a thermolysin-like zinc metalloendopeptidase, plays an important role in turning off peptide signalling events at the cell surface...
  11. ncbi Presynaptic localization of neprilysin contributes to efficient clearance of amyloid-beta peptide in mouse brain
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitama 351 0198, Japan
    J Neurosci 24:991-8. 2004
    ..Here, we report on the catabolic mechanism of Abeta at the presynaptic sites. Neprilysin, an Abeta-degrading enzyme, expressed by recombinant adeno-associated viral vector-mediated gene transfer, was ..
  12. ncbi Neuropeptide-stimulated cell migration in prostate cancer cells is mediated by RhoA kinase signaling and inhibited by neutral endopeptidase
    R Zheng
    Department of Urology, Urologic Oncology Research Laboratory, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY 10021, USA
    Oncogene 25:5942-52. 2006
    ..This work also identifies members of this signaling pathway as potential targets for rational pharmacologic manipulation of neuropeptide-stimulated migration of PC cells...
  13. ncbi Identification of the amyloid-degrading enzyme neprilysin in mouse islets and potential role in islet amyloidogenesis
    Sakeneh Zraika
    Division of Metabolism, Endocrinology anmd Nutrition, Department of Medicine, VA Puget Sound Health Care System, 1660 S Columbian Way, Seattle, WA 98108, USA
    Diabetes 56:304-10. 2007
    ..We sought to determine whether neprilysin, an amyloid-degrading enzyme, is present in islets and plays a role in the accumulation of amyloid fibrils...
  14. pmc Expression and functional profiling of neprilysin, insulin-degrading enzyme, and endothelin-converting enzyme in prospectively studied elderly and Alzheimer's brain
    Suqing Wang
    Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53705, USA
    J Neurochem 115:47-57. 2010
    ..The major Aβ-degrading enzymes are neprilysin (NEP), insulin-degrading enzyme (IDE), and endothelin-converting enzyme (ECE-1)...
  15. pmc Global brain delivery of neprilysin gene by intravascular administration of AAV vector in mice
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    Sci Rep 3:1472. 2013
    ..Stereotaxic infusion of neprilysin-encoding viral vectors into the hippocampus has been shown to decrease Aβ in AD-model mice, but more efficient ..
  16. ncbi Clearance of Alzheimer's Abeta peptide: the many roads to perdition
    R E Tanzi
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown 02129, USA
    Neuron 43:605-8. 2004
    ..This minireview will summarize pathways involved in the removal of cerebral Abeta, including enzymatic degradation and receptor-mediated efflux out of the brain...
  17. pmc Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes
    Takeshi Katsuda
    Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5 1 1 Tsukiji, Chuo Ku, Tokyo 104 0045, Japan
    Sci Rep 3:1197. 2013
    ..b>Neprilysin (NEP) is the most important Aβ-degrading enzyme in the brain...
  18. ncbi Availability of CD10 immunohistochemistry as a marker of breast myoepithelial cells on paraffin sections
    Suzuko Moritani
    Department of Pathology, Shiga University of Medical Science, Seta tsukinowa cho, Ohtsu, Japan
    Mod Pathol 15:397-405. 2002
    ..Combination of CD10 and SMA will provide more sophisticated information about presence or absence of myoepithelial cells in confusing breast lesions...
  19. pmc Cell surface expression of the major amyloid-β peptide (Aβ)-degrading enzyme, neprilysin, depends on phosphorylation by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) and dephosphorylation by protein phosphatase 1a
    Naomasa Kakiya
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    J Biol Chem 287:29362-72. 2012
    b>Neprilysin is one of the major amyloid-β peptide (Aβ)-degrading enzymes, the expression of which declines in the brain during aging...
  20. pmc Hypoxia-induced down-regulation of neprilysin by histone modification in mouse primary cortical and hippocampal neurons
    Zheng Wang
    Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    PLoS ONE 6:e19229. 2011
    ..Aβ metabolism is a dynamic process in the Aβ production and clearance that requires neprilysin (NEP) and other enzymes to degrade Aβ...
  21. pmc Peripheral delivery of a CNS targeted, metalo-protease reduces aβ toxicity in a mouse model of Alzheimer's disease
    Brian Spencer
    Department of Neurosciences, University of California San Diego, La Jolla, California, United States of America
    PLoS ONE 6:e16575. 2011
    ..We generated a lentivirus vector expressing the amyloid β-degrading enzyme, neprilysin, fused to the ApoB transport domain and delivered this by intra-peritoneal injection to amyloid protein ..
  22. ncbi Expression of Somatostatin, cortistatin, and their receptors, as well as dopamine receptors, but not of neprilysin, are reduced in the temporal lobe of Alzheimer's disease patients
    Manuel D Gahete
    Department of Cell Biology, Physiology and Immunology, University of Cordoba, and Instituto Maimónides de Investigación Biomédica de Córdoba, Cordoba, Spain
    J Alzheimers Dis 20:465-75. 2010
    ..real-time PCR the mRNA levels of SST/CST, their receptors (sst1-5 and DA receptors (drd1-5) in addition to neprilysin (a SST-regulated enzyme involved in Abeta degradation) in three regions of the temporal lobe, one of the ..
  23. ncbi Identification, proteomic profiling, and origin of ram epididymal fluid exosome-like vesicles
    Jean Luc Gatti
    Equipe Gamètes Males et Fertilité, URM 6175 INRA CNRS Université de TOURS Haras Nationaux, Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique de Nouzilly, Monnaie 37380, France
    Biol Reprod 72:1452-65. 2005
    ..proteins were identified and grouped into i) membrane-linked enzymes, such as dipeptidyl peptidase IV (DPP-IV), neprilysin (NEP), phosphodiesterase-I (E-NPP3), and protein G-beta; ii) vesicle-associated proteins, such as lactadherin (..
  24. ncbi Concise review: neutral endopeptidase (CD10): a multifaceted environment actor in stem cells, physiological mechanisms, and cancer
    Veronique Maguer-Satta
    Universite de Lyon, Lyon, F 69007, France
    Stem Cells 29:389-96. 2011
    ..This highlights the importance of understanding the role of CD10 in cancer SC. We will review the characteristics, main functions, and mechanism of action of CD10. Finally, we will review its clinical use and involvement in cancer...
  25. pmc Stromal cells from endometriotic lesions and endometrium from women with endometriosis have reduced decidualization capacity
    Petra A B Klemmt
    Nuffield Department of Obstetrics and Gynaecology, The Women s Centre, John Radcliffe Hospital, Oxford, United Kingdom
    Fertil Steril 85:564-72. 2006
    ..To evaluate the phenotype, proliferative, and differentiation capacities in vitro of stromal cells derived from peritoneal, ovarian, and deeply infiltrating endometriosis...
  26. pmc Neprilysin overexpression inhibits plaque formation but fails to reduce pathogenic Abeta oligomers and associated cognitive deficits in human amyloid precursor protein transgenic mice
    William J Meilandt
    Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA
    J Neurosci 29:1977-86. 2009
    ..Overexpression of the Abeta-degrading enzyme neprilysin in brains of human amyloid precursor protein (hAPP) transgenic mice decreases overall Abeta levels and amyloid ..
  27. pmc Trafficking CD11b-positive blood cells deliver therapeutic genes to the brain of amyloid-depositing transgenic mice
    Lori Lebson
    Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida 33612, USA
    J Neurosci 30:9651-8. 2010
    ..weekly infusions of the CD11b+ bone marrow cells transfected with a genetically engineered form of the protease neprilysin completely arrest amyloid deposition in an aggressively depositing transgenic model...
  28. ncbi Prognostic impact of germinal center-associated proteins and chromosomal breakpoints in poor-risk diffuse large B-cell lymphoma
    Gustaaf W van Imhoff
    Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    J Clin Oncol 24:4135-42. 2006
    ....
  29. ncbi Loss of CD10 (neutral endopeptidase) is a frequent and early event in human prostate cancer
    Stephen J Freedland
    Department of Urology, UCLA School of Medicine, Los Angeles, CA 90095 1738, USA
    Prostate 55:71-80. 2003
    ....
  30. ncbi Relationship between beta amyloid peptide generating molecules and neprilysin in Alzheimer disease and normal brain
    K Yasojima
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, V6T 1Z3, Vancouver, Canada
    Brain Res 919:115-21. 2001
    ..Presenilin-1 (PS-1) is intimately related to gamma-secretase. Once formed, Abeta is mainly broken down by neprilysin. To estimate vulnerability to Abeta senile plaque formation, we measured the relative mRNA levels of APP695, ..
  31. ncbi The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial
    Scott D Solomon
    Cardiovascular Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    Lancet 380:1387-95. 2012
    ..We assessed the efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), in patients with this disorder.
  32. ncbi Neutral endopeptidase 24.11 and dipeptidyl peptidase IV are both mediators of the degradation of glucagon-like peptide 1 in the anaesthetised pig
    A Plamboeck
    Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
    Diabetologia 48:1882-90. 2005
    ..Dipeptidyl peptidase IV (DPP-IV) is established as the primary inactivating enzyme, but the roles of other enzymes remain unclear...
  33. pmc Bioinformatic analysis of the neprilysin (M13) family of peptidases reveals complex evolutionary and functional relationships
    Nicholas D Bland
    Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK
    BMC Evol Biol 8:16. 2008
    The neprilysin (M13) family of endopeptidases are zinc-metalloenzymes, the majority of which are type II integral membrane proteins...
  34. pmc CD10 is a marker for cycling cells with propensity to apoptosis in childhood ALL
    G Cutrona
    Servizi di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, IST, Genoa, Italy, and Dipartimento di Oncologia, Biologia e Genetica, Universita di Genova, Genoa, Italy
    Br J Cancer 86:1776-85. 2002
    ....
  35. ncbi Abeta-degrading enzymes: modulators of Alzheimer's disease pathogenesis and targets for therapeutic intervention
    E A Eckman
    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA
    Biochem Soc Trans 33:1101-5. 2005
    ..and its concentration is determined in part by the activities of several degradative enzymes, including NEP (neprilysin), IDE (insulin-degrading enzyme), ECE-1 (endothelin-converting enzyme 1) and ECE-2, and probably plasmin...
  36. ncbi On the role of endothelin-converting enzyme-1 (ECE-1) and neprilysin in human breast cancer
    Martin Smollich
    Department of Obstetrics and Gynecology, University Hospital of Munster, Albert Schweitzer Str 33, 48149, Munster, Germany
    Breast Cancer Res Treat 106:361-9. 2007
    ..However, little is known about the relevance of endothelin-converting enzyme-1 (ECE-1) and ET-1 degrading neprilysin (NEP)...
  37. ncbi Structure of human neutral endopeptidase (Neprilysin) complexed with phosphoramidon
    C Oefner
    Pharma Preclinical Research, F Hoffmann La Roche Ltd, Basel, CH 4070, Switzerland
    J Mol Biol 296:341-9. 2000
    ..The inhibitor is bound to one side of this cavity and its binding mode provides a detailed understanding of the ligand-binding and specificity determinants...
  38. ncbi High CD10 expression in lymph node metastases from surgically treated prostate cancer independently predicts early death
    Achim Fleischmann
    Institute of Pathology, University of Bern, Bern, Switzerland
    Virchows Arch 458:741-8. 2011
    ..In conclusion, a high CD10 expression in prostate cancer predicts early death. This information is inherent in the primary tumors and in the lymph node metastases and might help to personalize patient management...
  39. ncbi Enhanced proteolytic clearance of plasma Aβ by peripherally administered neprilysin does not result in reduced levels of brain Aβ in mice
    John R Walker
    Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA
    J Neurosci 33:2457-64. 2013
    ..b>Neprilysin (NEP) is a zinc-dependent metalloprotease that is one of the key Aβ-degrading enzymes in the brain...
  40. ncbi Down-regulation of neprilysin (EC3.4.24.11) expression in vascular endothelial cells by laminar shear stress involves NADPH oxidase-dependent ROS production
    Paul A Fitzpatrick
    School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland
    Int J Biochem Cell Biol 41:2287-94. 2009
    b>Neprilysin (NEP, neutral endopeptidase, EC3.4.24.11), a zinc metallopeptidase expressed on the surface of endothelial cells, influences vascular homeostasis primarily through regulated inactivation of natriuretic peptides and bradykinin...
  41. ncbi Mammalian membrane metallopeptidases: NEP, ECE, KELL, and PEX
    A J Turner
    Department of Biochemistry and Molecular Biology, University of Leeds, U K
    FASEB J 11:355-64. 1997
    ..Inhibitors of ECE and NEP may have important therapeutic applications in cardiovascular and renal medicine...
  42. ncbi Abeta-degrading endopeptidase, neprilysin, in mouse brain: synaptic and axonal localization inversely correlating with Abeta pathology
    Shinjiro Fukami
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitama, Japan
    Neurosci Res 43:39-56. 2002
    ..Since neprilysin is the only rate-limiting catabolic peptidase proven by reverse genetics to participate in Abeta metabolism in ..
  43. ncbi Chemosensitization of androgen-independent prostate cancer with neutral endopeptidase
    Makoto Sumitomo
    Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan
    Clin Cancer Res 10:260-6. 2004
    ..We investigated whether neutral endopeptidase (NEP) could augment chemosensitivity to anticancer drugs by promoting protein kinase C (PKC)delta-mediated mitochondrial apoptosis in prostate cancer (PC) cells...
  44. ncbi Lentiviral vector neutral endopeptidase gene transfer suppresses prostate cancer tumor growth
    A Horiguchi
    Urologic Oncology Research Laboratory, Department of Urology, Weill Medical College of Cornell University, New York, NY 10021, USA
    Cancer Gene Ther 14:583-9. 2007
    b>Neprilysin (neutral endopeptidase, NEP) is a cell surface peptidase whose expression is lost in approximately 50% of prostate cancers (PC)...
  45. ncbi Effect of sodium valproate administration on brain neprilysin expression and memory in rats
    Natalia N Nalivaeva
    Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, United Kingdom
    J Mol Neurosci 46:569-77. 2012
    ..In the healthy brain, a group of amyloid-degrading enzymes including neprilysin (NEP) maintain Aβ levels at physiologically low concentrations but, with age and under some pathological ..
  46. ncbi Oxidized neprilysin in aging and Alzheimer's disease brains
    Deng Shun Wang
    Department of Neuroscience and Pathology Neuropathology, Mayo Clinic, Jacksonville, FL 32224, USA
    Biochem Biophys Res Commun 310:236-41. 2003
    ..b>Neprilysin (NEP) is a major enzyme for degradation of Abeta and changes in amount or activity of NEP may play a role in ..
  47. pmc Circulating neprilysin clears brain amyloid
    Yinxing Liu
    Department of Molecular and Cellular Biochemistry, University of Kentucky, College of Medicine, Lexington, KY 40536 0509, USA
    Mol Cell Neurosci 45:101-7. 2010
    The use of the peptidase neprilysin (NEP) as a therapeutic for lowering brain amyloid burden is receiving increasing attention...
  48. ncbi CD10 and CD34 in fetal and adult human hair follicles: dynamic changes in their immunohistochemical expression during embryogenesis and hair cycling
    E Poblet
    Department of Pathology and AECC Research Unit, Hospital General Universitario de Albacete, Albacete, Spain
    Br J Dermatol 159:646-52. 2008
    ..CD10 and CD34 have been detected in both epithelial and mesenchymal components of anagen human hair follicles...
  49. pmc Neprilysin-2 is an important β-amyloid degrading enzyme
    Daniel Hafez
    Department of Neuroscience, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064, USA
    Am J Pathol 178:306-12. 2011
    ..The Aβ-degrading enzyme neprilysin (NEP) is the best known target of these inhibitors...
  50. pmc Neprilysin, obesity and the metabolic syndrome
    K F Standeven
    Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK
    Int J Obes (Lond) 35:1031-40. 2011
    b>Neprilysin (NEP), a zinc metalloendopeptidase, has a role in blood pressure control and lipid metabolism...
  51. pmc Casein kinase 2 dependent phosphorylation of neprilysin regulates receptor tyrosine kinase signaling to Akt
    Martin Siepmann
    Department of Neurology, Molecular Cell Biology, University of Bonn, Bonn, Germany
    PLoS ONE 5:. 2010
    b>Neprilysin (NEP) is a type II membrane metalloproteinase that cleaves physiologically active peptides at the cell surface thus regulating the local concentration of these peptides available for receptor binding and signal transduction...
  52. ncbi Neprilysin activity in cerebrospinal fluid is associated with dementia and amyloid-β42 levels in Lewy body disease
    Walter Maetzler
    Center of Neurology, Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany
    J Alzheimers Dis 22:933-8. 2010
    ..b>Neprilysin (NEP) is an Aβ-degrading protein found at presynaptic terminals and in body fluids...
  53. ncbi Beta-amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases?
    Julie A Carson
    Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, UK
    J Neurochem 81:1-8. 2002
    ..Recent attention has focused on members of the neprilysin (NEP) family of zinc metalloproteinases in amyloid metabolism...
  54. pmc Neprilysin is identical to skin fibroblast elastase: its role in skin aging and UV responses
    Naoko Morisaki
    Kao Biological Science Laboratories, 2606 Akabane, Ichikaimachi, Haga, Tochigi 321 3497, Japan
    J Biol Chem 285:39819-27. 2010
    ..As there are similarities in the molecular weights and inhibitory profiles of HSF elastase and neprilysin (neutral endopeptidase 24...
  55. ncbi Declining expression of neprilysin in Alzheimer disease vasculature: possible involvement in cerebral amyloid angiopathy
    Mélanie Carpentier
    Departement de Biochimie, Faculte de Medecine, Universite de Montreal, Quebec, Canada
    J Neuropathol Exp Neurol 61:849-56. 2002
    Molecular, genetic, and pharmacological studies have shown that neprilysin (also called NEP) catabolizes amyloid beta peptides (A beta) in healthy conditions...
  56. ncbi Neprilysin and insulin-degrading enzyme levels are increased in Alzheimer disease in relation to disease severity
    James Scott Miners
    Dementia Research Group, Clinical Science at North Bristol, University of Bristol, Frenchay Hospital, Frenchay, Bristol, United Kingdom
    J Neuropathol Exp Neurol 68:902-14. 2009
    Experimental reduction of neprilysin (NEP) or insulin-degrading enzyme (IDE) in vivo exacerbates beta-amyloid accumulation in the brain...
  57. pmc Expression of neprilysin in skeletal muscle reduces amyloid burden in a transgenic mouse model of Alzheimer disease
    Yinxing Liu
    Department of Molecular and Cellular Biochemistry, University of Kentucky, College of Medicine, Lexington, Kentucky, USA
    Mol Ther 17:1381-6. 2009
    b>Neprilysin (NEP) is a zinc metallopeptidase that efficiently degrades the amyloid beta (Abeta) peptides believed to be involved in the etiology of Alzheimer disease (AD)...
  58. ncbi Stromal expression of CD10 in invasive breast carcinoma: a new predictor of clinical outcome
    Keiichi Iwaya
    First Department of Pathology, Tokyo Medical University, 160 8402 Shinjuku 6 1 1, Shinjuku ku, Tokyo, Japan
    Virchows Arch 440:589-93. 2002
    ..0059), and CD10 was the single significant prognostic factor for overall survival in the univariate analysis ( P=0.0021). These results suggest that stromal expression of CD10 in breast cancer is an important novel prognostic factor...
  59. ncbi The epigenetic effects of amyloid-beta(1-40) on global DNA and neprilysin genes in murine cerebral endothelial cells
    Kun Lin Chen
    Department of Neurology and The Topnotch Stroke Research Center, Taipei Medical University, 250 Wu Hsing Street, Taipei 110, Taiwan
    Biochem Biophys Res Commun 378:57-61. 2009
    ..It therefore remains largely unknown as to whether Abeta does in fact cause DNA methylation/demethylation. Neprilysin (NEP) is one of the enzymes responsible for Abeta degradation, with its expression decreasing in both Alzheimer ..
  60. ncbi Distinct subcellular expression patterns of neutral endopeptidase (CD10) in prostate cancer predict diverging clinical courses in surgically treated patients
    Achim Fleischmann
    Department of Pathology, University Medical Center Hamburg Eppendorf, Hamburg, Germany
    Clin Cancer Res 14:7838-42. 2008
    ..Neutral endopeptidase (CD10), an ectopeptidase bound to the cell surface, is thought to be a potential prognostic marker for prostate cancer...
  61. ncbi Herpes simplex virus RNAi and neprilysin gene transfer vectors reduce accumulation of Alzheimer's disease-related amyloid-beta peptide in vivo
    C S Hong
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, PA 15261, USA
    Gene Ther 13:1068-79. 2006
    ..HSV vectors expressing either (i) short hairpin RNA directed to the APP transcript (HSV-APP/shRNA), or (ii) neprilysin, an endopeptidase that degrades Abeta (HSV-neprilysin), substantially inhibited accumulation of Abeta...
  62. ncbi Regulation of steady-state beta-amyloid levels in the brain by neprilysin and endothelin-converting enzyme but not angiotensin-converting enzyme
    Elizabeth A Eckman
    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
    J Biol Chem 281:30471-8. 2006
    ..prevented in part by the activities of several degradative enzymes, including the endothelin-converting enzymes, neprilysin, insulin-degrading enzyme, and plasmin...
  63. pmc Long-term neprilysin gene transfer is associated with reduced levels of intracellular Abeta and behavioral improvement in APP transgenic mice
    Brian Spencer
    Department of Neurosciences, University of California San Diego, La Jolla, California 92093, USA
    BMC Neurosci 9:109. 2008
    ..The endopeptidase, neprilysin, has been implicated as a major Abeta degrading enzyme in mice and humans...
  64. ncbi Metabolism of amyloid-beta peptide and Alzheimer's disease
    Nobuhisa Iwata
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako Shi, Saitama 351 0198, Japan
    Pharmacol Ther 108:129-48. 2005
    ..b>Neprilysin is a rate-limiting peptidase involved in the physiological degradation of Abeta in the brain...
  65. ncbi Biochemical identification of the neutral endopeptidase family member responsible for the catabolism of amyloid beta peptide in the brain
    Y Takaki
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama 351 0198, Japan
    J Biochem 128:897-902. 2000
    ..We analyzed the brain-derived enzyme by means of immuno-depletion and gene disruption, and demonstrate here that neprilysin accounts for the majority of the Abeta-degrading activity...
  66. pmc Estrogen stimulates degradation of beta-amyloid peptide by up-regulating neprilysin
    Kaiwei Liang
    State Key Lab of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China
    J Biol Chem 285:935-42. 2010
    ..we provide evidence that estrogen promotes Abeta degradation mainly through a principal Abeta degrading enzyme, neprilysin, in neuroblastoma SH-SY5Y cells...
  67. pmc A human postnatal lymphoid progenitor capable of circulating and seeding the thymus
    Emmanuelle M Six
    Institut National de la Sante et de la Recherche Medicale INSERM, U768, 75015 Paris, France
    J Exp Med 204:3085-93. 2007
    ..Moreover, they belong to the most immature thymocyte population. Collectively, these findings unravel the existence of a postnatal lymphoid-polarized population that is capable of migrating from the BM to the thymus...
  68. ncbi Ginsenoside Rg3 promotes beta-amyloid peptide degradation by enhancing gene expression of neprilysin
    LingLing Yang
    Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan 250012, Shandong, China
    J Pharm Pharmacol 61:375-80. 2009
    ..Recent evidence has shown that neprilysin (NEP) is the rate-limiting enzyme in the Abeta degradation in the brain. Ginseng, the root of Panax ginseng C.A...
  69. ncbi Utility of CD10 in distinguishing between endometrial stromal sarcoma and uterine smooth muscle tumors: an immunohistochemical comparison of 34 cases
    P G Chu
    Division of Pathology, City of Hope National Medical Center, Duarte, California 91010, USA
    Mod Pathol 14:465-71. 2001
    ..We conclude that in combination with SMA, MSA, and desmin, CD10 is a useful immunohistochemical marker in the differential diagnosis of ESS versus UCL or ULS...
  70. ncbi Human neprilysin is capable of degrading amyloid beta peptide not only in the monomeric form but also the pathological oligomeric form
    Hyoe Kanemitsu
    Department of Neuroscience, Graduate School of Medicine Osaka City University, 1 4 3 Asahimachi, Abeno Ku, Osaka 545 8585, Japan
    Neurosci Lett 350:113-6. 2003
    ..Here we studied neprilysin, a putative proteolytic enzyme for Abeta, and found that it degraded not only monomeric but also oligomeric ..
  71. pmc CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung
    M A Shipp
    Department of Medicine, Harvard Medical School, Boston, MA 02115
    Proc Natl Acad Sci U S A 88:10662-6. 1991
    ..Since SCCa of the lung occurs almost exclusively in cigarette smokers and cigarette smoke inactivates CD10/NEP, decreased cell surface CD10/NEP enzymatic activity may be causally related to the development of SCCa of the lung...
  72. pmc Peripherally expressed neprilysin reduces brain amyloid burden: a novel approach for treating Alzheimer's disease
    Hanjun Guan
    Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky 40536 0509, USA
    J Neurosci Res 87:1462-73. 2009
    ..a novel strategy for lowering amyloid burden in the brain by peripherally expressing the Abeta-degrading enzyme neprilysin on leukocytes in the 3xTg-AD mouse model of Alzheimer's disease...
  73. ncbi HIV-1 Tat inhibits neprilysin and elevates amyloid beta
    Hans C Rempel
    Department of Laboratory Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, USA
    AIDS 19:127-35. 2005
    ..lengthened the life expectancy of individuals infected with HIV-1, we investigated the affect of HIV-1 Tat, a viral transactivating transcription factor, on Abeta degradation in the brain by neprilysin (NEP), a neuronal endopeptidase.
  74. ncbi Somatostatin regulates brain amyloid beta peptide Abeta42 through modulation of proteolytic degradation
    Takashi Saito
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    Nat Med 11:434-9. 2005
    ..pathogenic agent of Alzheimer disease, in the brain through modulating proteolytic degradation catalyzed by neprilysin. Among various effector candidates, only somatostatin upregulated neprilysin activity in primary cortical ..
  75. ncbi Human adipose tissue cells keep tight control on the angiotensin II levels in their vicinity
    Petra Schling
    Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz Josef Strauss Allee 11, Germany
    J Biol Chem 277:48066-75. 2002
    ..The endopeptidase could be identified as neprilysin expressed on the surface of both preadipocytes and adipocytes...
  76. ncbi Synergy in tumor suppression by direct interaction of neutral endopeptidase with PTEN
    Makoto Sumitomo
    Urological Oncology Research Laboratory, Department of Urology, Joan and Stanford I Weill Medical College of Cornell University, New York, NY 10021, USA
    Cancer Cell 5:67-78. 2004
    ..This study demonstrates a molecular cooperation between NEP and PTEN tumor suppressors in which NEP constitutively recruits and activates PTEN to inhibit the PI3K/Akt oncogenic pathway...
  77. ncbi Antioxidants inhibit fatty acid and glucose-mediated induction of neutral endopeptidase gene expression in human microvascular endothelial cells
    Pornprom Muangman
    Department of Surgery, University of Washington, Harborview Medical Center, Seattle, WA 98104, USA
    J Am Coll Surg 200:208-15. 2005
    ..We have shown that unsaturated fatty acids and glucose upregulate NEP activity in human microvascular endothelial cells (HMECs) and that vitamins E and C reduce this effect...
  78. ncbi Circulating activities of angiotensin-converting enzyme, its homolog, angiotensin-converting enzyme 2, and neprilysin in a family study
    Gillian I Rice
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT United Kingdom
    Hypertension 48:914-20. 2006
    ..The aim of this study was to determine the heritability of circulating ACE, ACE2, and neprilysin (NEP), which may also be a regulator of BP, in a family study, and to determine covariates that contribute to ..
  79. ncbi Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE)
    Milton Packer
    Division of Circulatory Physiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Circulation 106:920-6. 2002
    ..Combined inhibition of the angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) may produce greater benefits in heart failure than ACE inhibition alone...
  80. ncbi Neutral endopeptidase inhibits neuropeptide-mediated transactivation of the insulin-like growth factor receptor-Akt cell survival pathway
    M Sumitomo
    Urologic Oncology Research Laboratory, Department of Urology, Weill Medical College of Cornell University, New York, NY 10021, USA
    Cancer Res 61:3294-8. 2001
    ..These data show that the neuropeptides ET-1 and bombesin stimulate ligand-independent activation of the IGF-IR, which results in Akt activation, and that this cross-communication between GPCR and IGF-IR signaling is inhibited by NEP...
  81. pmc Neutral endopeptidase inhibits prostate cancer cell migration by blocking focal adhesion kinase signaling
    M Sumitomo
    Urologic Oncology Research Laboratory, Department of Urology, and Department of Pathology, Weill Medical College of Cornell University, New York, New York, USA
    J Clin Invest 106:1399-407. 2000
    ....
  82. ncbi Neprilysin II: A putative novel metalloprotease and its isoforms in CNS and testis
    T Ouimet
    Unité de Neurobiologie et Pharmacologie Moléculaire U109 de L INSERM, Centre Paul Broca, 2ter rue d Alesia, Paris, 75014, France
    Biochem Biophys Res Commun 271:565-70. 2000
    ..In brain, NEPII is expressed heterogeneously among several neuronal populations and according to a pattern grossly complementary to that of NEP...
  83. ncbi CD10 expression in stromal cells of oral cavity squamous cell carcinoma: a clinic and pathologic correlation
    A Piattelli
    Dental School, University of Chieti Pescara, Chieti, Italy
    Oral Dis 12:301-4. 2006
    ..CD10 is expressed on the majority of follicle-center lymphomas and Burkitt lymphomas. CD10 has also been shown to be present in a variety of other neoplasms...
  84. ncbi B lymphopoiesis is active throughout human life, but there are developmental age-related changes
    Maria Isabel D Rossi
    Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA
    Blood 101:576-84. 2003
    ..Dramatic changes in human B lymphopoiesis occur early in life, and more information is required to construct a probable sequence of differentiation events prior to the acquisition of CD10...
  85. pmc A neprilysin polymorphism and amyloid-beta plaques after traumatic brain injury
    Victoria E Johnson
    Penn Center for Brain Injury and Repair, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurotrauma 26:1197-202. 2009
    ..association between amyloid deposition acutely after TBI and a genetic polymorphism of the AB-degrading enzyme, neprilysin (n = 81). We found that the length of the GT repeats in AB-accumulators was longer than in non-accumulators...
  86. ncbi Expression of neuropeptide-degrading enzymes in alopecia areata: an immunohistochemical study
    M Toyoda
    Department of Dermatology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930 0194, Japan
    Br J Dermatol 144:46-54. 2001
    ..However, there has been little substantial evidence of specific participation of cutaneous neurogenic factors in the disease process...
  87. pmc Gleevec increases levels of the amyloid precursor protein intracellular domain and of the amyloid-beta degrading enzyme neprilysin
    Yvonne S Eisele
    Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen, D 72076 Tubingen, Germany
    Mol Biol Cell 18:3591-600. 2007
    ..with the increase in AICD, Gleevec leads to elevated mRNA and protein levels of the Abeta-degrading enzyme neprilysin, a potential target gene of AICD-regulated transcription...
  88. ncbi Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study
    Luis Miguel Ruilope
    Division of Hypertension, Hospital 12 de Octubre, Madrid, Spain
    Lancet 375:1255-66. 2010
    LCZ696 is a first-in-class inhibitor of the angiotensin II receptor and neprilysin. We aimed to establish whether the dual actions of LCZ696 lead to further lowering of blood pressure, compared with the angiotensin-receptor blocker ..
  89. pmc Improved learning and memory in aged mice deficient in amyloid beta-degrading neutral endopeptidase
    Thomas Walther
    Department of Cardiology, Charite University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany
    PLoS ONE 4:e4590. 2009
    Neutral endopeptidase, also known as neprilysin and abbreviated NEP, is considered to be one of the key enzymes in initial human amyloid-beta (Abeta) degradation...
  90. ncbi Effects of neprilysin chimeric proteins targeted to subcellular compartments on amyloid beta peptide clearance in primary neurons
    Emi Hama
    Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    J Biol Chem 279:30259-64. 2004
    b>Neprilysin (NEP) is a rate-limiting amyloid beta peptide (Abeta)-degrading enzyme in the brain...
  91. ncbi Changes with age in the activities of beta-secretase and the Abeta-degrading enzymes neprilysin, insulin-degrading enzyme and angiotensin-converting enzyme
    J Scott Miners
    Dementia Research Group, Institute of Clinical Neurosciences, Clinical Science at North Bristol, University of Bristol, Bristol, UK
    Brain Pathol 20:794-802. 2010
    ..We measured BACE-1 activity and the levels and activities of neprilysin (NEP), insulin-degrading enzyme (IDE) and angiotensin-converting enzyme (ACE) in normal control brains (16 years-..
  92. ncbi Age-dependent decline of neprilysin in Alzheimer's disease and normal brain: inverse correlation with A beta levels
    E Hellström-Lindahl
    Karolinska Institute, Department of Neurobiology, Care Sciences and Society, Division of Molecular Neuropharmacology, Geriatric lab, Novum, Floor 4, S 141 86 Stockholm, Sweden
    Neurobiol Aging 29:210-21. 2008
    ..b>Neprilysin has been shown to be an important enzyme to degrade A beta in brain...
  93. ncbi Androgens regulate neprilysin expression: role in reducing beta-amyloid levels
    Mingzhong Yao
    Davis School of Gerontology, University of Southern California, Los Angeles, California 90089 0191, USA
    J Neurochem 105:2477-88. 2008
    ..In this study, we investigated the role of the Abeta-catabolizing enzyme neprilysin (NEP) in this process...
  94. ncbi Immunoreactivity of CD10 and inhibin alpha in differentiating hemangioblastoma of central nervous system from metastatic clear cell renal cell carcinoma
    Shih Ming Jung
    Department of Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
    Mod Pathol 18:788-94. 2005
    ..In conclusion, in addition to the immunostaining of inhibin A, CD10 is a superior marker for distinguishing between a hemangioblastoma and a metastatic clear cell renal cell carcinoma...
  95. ncbi Immunocapture-based fluorometric assay for the measurement of neprilysin-specific enzyme activity in brain tissue homogenates and cerebrospinal fluid
    James Scott Miners
    Dementia Research Group, Institute of Clinical Neurosciences, Clinical Science at North Bristol, University of Bristol, Frenchay Hospital, Frenchay, Bristol BS16 1LE, UK
    J Neurosci Methods 167:229-36. 2008
    b>Neprilysin, a zinc-metalloendopeptidase, has important roles in the physiology and pathology of many diseases such as hypertension, cancer and Alzheimer's disease...
  96. ncbi Neprylisin decreases uniformly in Alzheimer's disease and in normal aging
    Roberta Russo
    Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Via De Toni 5, 16132 Genoa, Italy
    FEBS Lett 579:6027-30. 2005
    ..We investigated whether a decrease in neprilysin levels contributes to the accumulation of amyloid deposits not only in AD but also in the normal aging...
  97. ncbi Neutral endopeptidase neprilysin is copurified with Na,K-ATPase from rabbit outer medulla and hydrolyzes its α-subunit
    M A Groubman
    Department of Biochemistry, Lomonosov Moscow State University, Russia
    Biochemistry (Mosc) 75:1281-4. 2010
    ..chromatography/tandem mass spectrometry (LC/MS/MS) analysis showed that the neutral membrane-bound endopeptidase neprilysin is located in one protein band together with the Na,K-ATPase α-subunit...
  98. ncbi CD10 is a marker for normal and neoplastic endometrial stromal cells
    Toshihiko Toki
    Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Asahi, Matsumoto, Japan
    Int J Gynecol Pathol 21:41-7. 2002
    ..These data suggest that diffuse CD10 staining is characteristic of normal and neoplastic endometrial stromal cells, unless they are decidualized...
  99. pmc Neprilysin null mice develop exaggerated pulmonary vascular remodeling in response to chronic hypoxia
    Edward C Dempsey
    Cardiovascular Pulmonary Research Laboratory B 133, University of Colorado Denver, 12700 E 19 Ave, Aurora, CO 80046, USA
    Am J Pathol 174:782-96. 2009
    b>Neprilysin is a transmembrane metalloendopeptidase that degrades neuropeptides that are important for both growth and contraction...
  100. ncbi Neutral endopeptidase inhibits prostate cancer tumorigenesis by reducing FGF-2-mediated angiogenesis
    A Horiguchi
    Urologic Oncology Research Laboratory, Department of Urology, Weill Medical College of Cornell University, New York, NY 10021, USA
    Prostate Cancer Prostatic Dis 11:79-87. 2008
    ..05). Our data suggest that stable expression of NEP in DU145 cells inhibits prostate cancer tumorigenicity by inhibiting angiogenesis, with a probable mechanism being proteolytic inactivation of FGF-2...
  101. ncbi Ontogeny, regional and cellular distribution of the novel metalloprotease neprilysin 2 in the rat: a comparison with neprilysin and endothelin-converting enzyme-1
    P Facchinetti
    Unité de Neurobiologie et Pharmacologie Moléculaire U573 de l INSERM, Centre Paul Broca, 2ter rue d Alesia, 75014 Paris, France
    Neuroscience 118:627-39. 2003
    The localisation of the gene transcripts of a recently discovered peptidase, neprilysin 2 (NEP2), was established by in situ hybridisation in rat tissues during development and adulthood...

Research Grants63

  1. NEURAL REGULATION OF PANCREATIC FUNCTION
    KIMBERLY SAUNDERS KIRKWOOD; Fiscal Year: 2012
    ....
  2. Neprilysin and Pulmonary Vascular Remodeling: Cellular and Molecular Mechanisms
    EDWARD CHARLES DEMPSEY; Fiscal Year: 2013
    ..b>Neprilysin (NEP) is a transmembrane protein with a cell surface peptidase activity that degrades select pro- and anti-..
  3. Insulin Resistance and Vascular Complications in Obesity and Type 2 Diabetes
    Mark A Yorek; Fiscal Year: 2013
    ..Objective 2: Determine whether type 2 diabetes reduces the benefits of Ilepatril treatment due to higher levels of oxidative stress and/o degradation of vasoactive peptides. ..
  4. Prevention of Diabetic Neuropathy with ACE Inhibitors
    MARK ANTHONY YOREK; Fiscal Year: 2012
    ..If successful, these studies could provide a rationale for designing clinical studies to further test the efficacy of angiotensin converting enzyme and/or vasopeptidase inhibitor treatment in human diabetic neuropathy. ..
  5. Transgenic Mice, Inflammation &the Alzheimer Phenotype
    Marcia N Gordon; Fiscal Year: 2012
    ..b>Neprilysin is a major amyloid degrading protease, and a prime candidate for use in anti-amyloid gene therapy...
  6. Calcitonin for treating X-linked hypophosphatemia
    KARL LEONARD INSOGNA; Fiscal Year: 2012
    ..This approach, unlike conventional treatment, addresses the underlying pathophysiology in this disorder and would represent the first therapeutic advance for XLH in 30 years. ..
  7. CHADSS: Chagas Disease Scan Study
    Jamary Oliveira-Filho; Fiscal Year: 2013
    ..Biomarkers orosomucoid, neprilysin, interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) were identified as diagnostic and therapeutic ..
  8. Impact of Neprilysin on Islet Function
    Sakeneh Zraika; Fiscal Year: 2013
    ..b>Neprilysin (NEP) is a widely expressed plasma membrane peptidase that we have shown is increased in islets with prolonged ..
  9. Somatostatin Agonist Treatment for Cognitive Aging and Dementia
    Ken A Witt; Fiscal Year: 2010
    ..Somatostatin has been shown to be decreased in humans suffering from AD and specifically regulates neuronal neprilysin activity, a potent Ab-degrading enzyme...
  10. Neprilysin and Peripheral Clearance of Amyloid Peptides
    Louis B Hersh; Fiscal Year: 2010
    ..We have exploited this "sink effect" by showing that the peptidase neprilysin, when expressed peripherally on leukocytes reduced amyloid beta peptide levels in the brain of a hAPP transgenic ..
  11. SUBSTANCE P-MEDIATED CARDIOVASCULAR INFLAMMATION
    William Weglicki; Fiscal Year: 2009
    ..abstract_text> ..
  12. Untangling Amyloid Plaques With Proteases
    Jin Moo Lee; Fiscal Year: 2010
    ..of some of these proteases in vivo have resulted in increased steady-state levels of brain A? in mice, including neprilysin (NEP), insulin-degrading enzyme (IDE), endothelin-converting enzyme (ECE)...
  13. Impaired Protein Degradation Pathways in Cardiac Proteinopathy
    Patrick M McLendon; Fiscal Year: 2013
    ..routes can affect aberrant protein aggregation in CryABR120G-based DRM: 1) PAO removal/degradation by neprilysin, a protein shown to degrade soluble oligomers in similar diseases, will impact favorably on CryABR120G ..
  14. Protein-Protein Interactions in the Biology of Beta-APP
    Dennis J Selkoe; Fiscal Year: 2012
    ..central or peripheral expression of engineered versions of two well-characterized Abeta degrading proteases - neprilysin and insulin degrading enzyme (IDE) -can safely and effectively decrease cerebral Abeta burden in mouse models of ..
  15. The role of neprilysin in pancreatic beta-cell dysfunction and death
    Sakeneh Zraika; Fiscal Year: 2013
    ..The protein neprilysin, a component ofthe renin-angiotensin system (RAS), has been shown in non-islet tissues to be upregulated with ..
  16. OZONE INDUCED AIRWAY EPITHELIAL HYPERPROLIFERATION
    CHRISTOPHER MURLAS; Fiscal Year: 1999
    ..It is hoped this information will increase their understanding concerning the importance of cell NEP expression in modulating airway epithelial mitogenesis, especially as it may relate to airway disease due to repeated ozone exposure. ..
  17. LXR and PPARgamma mediated Abeta clearance mechanisms
    Gary E Landreth; Fiscal Year: 2011
    ..We show that lipidated forms of ApoE facilitate the intracellular degradation of A peptides by microglia through neprilysin- dependent proteolysis...
  18. TBI: Uncovering Mechanisms of AD-like pathology
    DOUGLAS HAMILTON SMITH; Fiscal Year: 2013
    ..Indeed, we have shown in preliminary data using multiple models that neprilysin, the primary Ass degrading enzyme, may have a key role in clearing Ass following injury...
  19. Genetically Modified Stem Cells For Alzheimer's Disease Therapy
    Xiaofeng Xia; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Stem cell therapy and Ab clearance through neprilysin (NEP) gene delivery have recently been shown to be effective treatments on mouse Alzheimer's Disease (AD) models...
  20. Pathogenesis and Impact of Islet Amyloid
    STEVEN EMANUEL KAHN; Fiscal Year: 2013
    ..Our recently developed data demonstrate that two proteases, neprilysin and matrix metalloproteinase-9 (MMP-9), normally produced by the islet, can limit fibril formation by IAPP...
  21. African American Alzheimer's Progression Markers - CSF and Neuro-Imaging
    WILLIAM TZU LUNG HU; Fiscal Year: 2013
    ..ICAM-1 levels is uniquely found in 16-20% of AA, and these subjects may have impaired downstream activation of neprilysin, an Ab-degrading enzyme...
  22. Alzheimer-Like Pathologies Following Traumatic Brain Injury in Older Individuals
    DOUGLAS HAMILTON SMITH; Fiscal Year: 2012
    ..More recently, we have identified that the A2- degrading enzyme, neprilysin, may play an important role in the emergence of plaques...
  23. The Role of Cathepsin B and Cystatin C in Alzheimer's Disease
    Li Gan; Fiscal Year: 2013
    ..However, unlike some other Abeta degradation enzymes, such as neprilysin (NEP, an endopeptidase with optimal activity at a neutral pH), CatB truncates Abeta at the C-terminus with ..
  24. Investigating the role of BDNF in the Stem Cell-mediated Restoration of Cognition
    NICHOLAS ALAN CASTELLO; Fiscal Year: 2011
    ..and whether efficacy can be improved by engineering NSCs to express an AD pathology-reducing enzyme, neprilysin. Recent stem cell-based approaches to treating Alzheimer's disease have been shown to reverse memory loss ..
  25. RENAL FUNCTION AND BLOOD PRESSURE CONTROL IN PREGNANCY
    Edmond Quillen; Fiscal Year: 2000
    ..These studies should improve our understanding to the integrative responses of estrogens, ANF and NO during pregnancy. ..
  26. LUNG AND AIRWAY AFFERENTS AND THEIR REFLEX ROLE
    JOHN COLERIDGE; Fiscal Year: 1992
    ....
  27. Vasopeptidases and Beta Amyloid Accumulation
    Christopher Eckman; Fiscal Year: 2009
    ..In addition, inhibitors of two other vasopeptidases, neprilysin (NEP) and endothelin-converting enzyme (ECE), are currently in preclinical and clinical development as are ..
  28. NEUROGENIC MECHANISMS OF INTESTINAL INFLAMMATION
    Eileen Grady; Fiscal Year: 2006
    ..Together, the results of these experiments will provide new insights into peptide signaling, generate novel information about mechanisms of intestinal inflammation, and suggest new strategies for therapy. ..
  29. Prevention of Diabetic Neuropathy with ACE Inhibitors
    Mark Yorek; Fiscal Year: 2007
    ..If successful, these studies could provide a rationale for designing clinical studies to further test the efficacy of ACE inhibitor treatment in human DN. ..
  30. NEUROPEPTIDASES AND CAROTID BODY FUNCTIONS
    Ganesh Kumar; Fiscal Year: 2000
    ..These studies may also yield new information in the development of enzyme based therapeutic agents in the treatment of hypoxemia, associated with high altitude adaptation and chronic obstructive lung diseases. ..
  31. A screen for small molecule inhibitors of soluble Abeta oligomer assembly
    Harry LeVine; Fiscal Year: 2007
    ..with compound, will be screened with trypsin, and if positive, digested with insulin-degrading enzyme and neprilysin, proteases believed to degrade Abeta peptides in vivo...
  32. Selected Peptidases and Pulmonary Vascular Remodeling in Chronic Obstructive Pulm
    EDWARD DEMPSEY; Fiscal Year: 2009
    ..We have shown that one of these peptidases, Neprilysin (NEP), is an important determinatn of susceptability to chronic hypoxic PHTN...
  33. REGULATION OF NEUTROPHIL CHEMOTAXIS IN INFLAMMATION
    RICHARD PAINTER; Fiscal Year: 1993
    ..Other useful reagents for these studies will include antibodies to the receptor or any assessory proteins (e.g. Gn and selected cytoskeletal proteins)...
  34. NEUTRAL PROTEASES IN LUNG CANCER
    Margaret Shipp; Fiscal Year: 1993
    ..o correlate in vitro observations and studies in animal models with clinical findings, specimens from patients with both malignant and non-malignant lesions of the lung will be evaluated for CD10/NEP and BLP expression...
  35. DESIGN OF SUICIDE INHIBITORS FR ENKEPHALINASE
    ODILE SAID NEJAD; Fiscal Year: 1991
    ..These compounds will then be evaluated for their time-dependent inactivation of enkephalinase to test the efficacy of the approach...
  36. PEPTIDE PROCESSING ENZYMES IN THE PLACENTA
    Sandra Reznik; Fiscal Year: 2002
    ..Specific aim 3 will test the hypothesis that the novel placental proteins also have nonenzymatic functions. ..
  37. NEUTRAL ENDOPEPTIDASE INACTIVATION IN ADVANCED PROSTATE
    David Nanus; Fiscal Year: 2005
    ..abstract_text> ..
  38. METABOLISM OF PEPTIDES BY HUMAN LUNG ENZYMES
    ERVIN ERDOS; Fiscal Year: 1993
    ..Specific inhibitors of peptidases will also be used to characterize the enzymes involved...
  39. Antagonism of PAMP, a potent angiogenic factor
    David Wilson; Fiscal Year: 2004
    ..PAMP and its derivatives are rapidly degraded in vivo by neprilysin. Because neprilysin only degrades peptides <3,000 daltons, we propose to stabilize the PAMP-antagonist by ..
  40. The role of neprilysin in pancreatic beta-cell dysfunction and death
    Sakeneh Zraika; Fiscal Year: 2010
    ..The protein neprilysin, has been shown in non-islet tissues to be upregulated with the chronically elevated glucose and fat levels seen ..
  41. Biological Significance of Oxidized Neprilysin
    Dengshun Wang; Fiscal Year: 2007
    ..The long-term objective of this study is to understand the biological significance of oxidative modification of neprilysin on amyloid deposition in aging and Alzheimer's disease (AD)...
  42. Neprilysin and Abeta-degradation in Alzheimer's disease
    Mark Kindy; Fiscal Year: 2005
    ..Recent studies indicate that the neutral endopeptidase neprilysin plays an important role in the degradation of Abeta(1-42) in the brain...
  43. REGULATION AND FUNCTION OF ANGIOTENSIN (1-7)
    Mark Chappell; Fiscal Year: 1999
    ..converting enzyme inhibition (which attenuates renal damage) augments the renal excretion of Ang-(1-7), and neprilysin (endopeptidase 24.11) inhibition reduces the excretion of Ang-(1-7), but augments Ang I and Ang II...
  44. Intranasal Tat: A Mouse Model for NeuroAIDS and Aging
    William Frey; Fiscal Year: 2004
    ..My Co-Investigator has new data to show that in vitro, HIV-1 Tat inhibits a major catabolizing enzyme, neprilysin, and increases amyloid beta (Abeta)...
  45. PREDICTORS OF RECURRENT STROKE IN THE PROGRESS STUDY
    Duncan Campbell; Fiscal Year: 2003
    ..In addition, plasma markers that predict risk of recurrent stroke may indicate novel therapies to prevent this condition. ..
  46. CHOLINE ACETYLTRANSFERASE
    Louis Hersh; Fiscal Year: 2004
    ....
  47. Estrogen, ACE2 and Salt-Sensitivity
    Mark Chappell; Fiscal Year: 2008
    ..Lewis strain. ..
  48. Estrogen, androgen, neprilysin, and amyloid peptides.
    Louis Hersh; Fiscal Year: 2008
    ..We recently found that ovariectomy in rats leads to a decrease in the activity of the peptidase neprilysin, and that ovariectomy followed by estrogen replacement increases neprilysin gene transcription and neprilysin ..
  49. Clin.Relevance of Circulat.Tumor Cells in Bladder Cancer
    Iman Osman; Fiscal Year: 2004
    ..abstract_text> ..
  50. Robotics Extraction System/HPLC for Shared Resource Lab
    Mark Chappell; Fiscal Year: 2005
    ..abstract_text> ..
  51. Micellar VIP Nanoparticles for Rheumatoid Arthritis
    Israel Rubinstein; Fiscal Year: 2007
    ..abstract_text> ..
  52. OXIDATIVE STRESS AND ANTIOXIDANTS IN IRON OVERLOAD
    William Bernard Weglicki; Fiscal Year: 2010
    ..The proposed studies may reveal potential benefits of using Ang II receptor blockade and lysosomotropic/antioxidant agents as adjunct therapy for iron-overloaded patients. ..
  53. Use of bone marrow stem cells to treat Alz. Dis
    Louis Hersh; Fiscal Year: 2005
    ..AD in which bone marrow stem cells are infected with a lentiviral vector directing expression of the peptidase neprilysin. The infected bone marrow cells are then transplanted to a recipient whereby the recipient will express ..
  54. SUBSTANCE P-MEDIATED CARDIOVASCULAR INFLAMMATION
    William Weglicki; Fiscal Year: 2007
    ..The hypotheses to be pursued in the Research Plan are outlined in Illustration 1. The potential relevance of clinical MgD to proinflammatory events in heart failure and other disease processes is addressed in the text. ..
  55. ATHEROGENESIS AND THE BONE MARROW ANGIOTENSIN SYSTEM
    Carlos Ferrario; Fiscal Year: 2004
    ..The proposed research will uncover novel mechanisms of atherogenesis that may have significant impact in the development of new therapeutic modalities applicable to cardiovascular and blood vessel diseases. ..
  56. Cardiomyopathy: Pro-Oxidant Role of Zidovudine (AZT)
    William Weglicki; Fiscal Year: 2007
    ..The proposed iron chelation and antibiotic intervention strategies may lead to adjunct therapies aimed at lessen AZT-related cardiovascular toxicity. [unreadable] [unreadable]..
  57. Neprilysin Apoptosis and Hypoxic Pulmonary Hypertension
    EDWARD DEMPSEY; Fiscal Year: 2008
    ..Susceptibility to apoptosis is likely an important determinant. Neprilysin (NEP) is a key cell surface peptidase involved in the degradation of vasoactive neuropeptides...
  58. Gut Hormones/Other Circulatory Regulators of Appetite
    Stephen Bloom; Fiscal Year: 2006
    ..Obesity produces over 6,000 excess deaths a week in the USA alone, yet there is no really effective treatment. This meeting is to advance the most promising approach to a safe practical therapy seen in the last 50 years. ..
  59. OHSU Medical Scientist Training Program
    David Jacoby; Fiscal Year: 2008
    ..D-Ph.D. Committee actively involved in student selection, mentoring, and policy formation together will provide a strong foundation to ensure the success of this program. ..
  60. Oxidative Stress And Sympathetic Nerve Activity
    Vito Campese; Fiscal Year: 2006
    ..If our hypothesis were to be correct, administration of inhibitors of the renin-angiotensin system particularly if combined with antioxidants should result in better control of BP in these models. ..
  61. Regulation of Slo Splicing in the Urogenital Systme
    Kelvin Davies; Fiscal Year: 2006
    ..This research project will allow Dr. Davies to develop a thorough understanding of urogenital physiology, while at the same time allowing him to utilize his experience in molecular biology. ..
  62. The gastrintestinal physiology of cholecystokinin
    Joseph Reeve; Fiscal Year: 2008
    ..The data collected will be used to predict amino acid substitutions that could increase binding of agonists to the CCK-A receptor. We will mutate the receptor with substitutions predicted to enhance binding to test our model. ..