Neprilysin II: A Putative Novel Metalloprotease and Its Isoforms in CNS and Testis

Ouimet, Tanja; Facchinetti, Patricia; Rose, Christiane; Bonhomme, Marie-Chantal; Gros, Claude P.; Schwartz, Jean‐Charles

doi:10.1006/bbrc.2000.2664

Cited by 49 publications

(14 citation statements)

References 22 publications

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“…This is contrary to NEP2 expression observed in rats as little to no NEP2 was found in the caudate by in-situ hybridization [34]. However, significant (but relatively lower) levels of NEP2 were found by reverse-transcription-PCR in the rat caudate [35]. …”

Section: Discussionmentioning

confidence: 85%

Altered NEP2 Expression and Activity in Mild Cognitive Impairment and Alzheimer's Disease

Huang

Hafez

James

et al. 2012

JAD

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Neprilysin-2 (NEP2), a close homolog of neprilysin (NEP), degrades amyloid-β (Aβ) and serves an important role in clearing Aβ in vivo. We measured NEP2 and NEP mRNA levels from non-impaired (NI), mild cognitive impaired (MCI), and clinical Alzheimer’s disease (AD) subjects in the mid-temporal gyrus, mid-frontal gyrus, caudate, and cerebellum. NEP2 activity levels were also determined. Our results indicate that NEP2 and NEP mRNA expression is altered in MCI subjects relative to NI subjects in AD-susceptible regions. NEP2 enzymatic activity was lowered in association with MCI and AD and was positively associated with level of cognitive function, independent of diagnostic category. Our finding that NEP2 expression and activity are altered in MCI is significant as these changes may potentially serve as preclinical markers for AD and reduced NEP2 activity may be associated with the development of AD.

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Section: Discussionmentioning

confidence: 85%

Altered NEP2 Expression and Activity in Mild Cognitive Impairment and Alzheimer's Disease

Huang

Hafez

James

et al. 2012

JAD

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“…NEP and ACE have been reported to reside predominantly on the cell surface, although a soluble form of NEP is also present in serum and cerebral spinal fluid (43)(44)(45)(46). A recently identified thiorphan-sensitive NEP homo-logue SEP/NL1/NEPII is expressed both as a membrane-bound and secreted protease (47)(48)(49). We evaluated a role for NEP and ACE in H4 neuroglioma cells using more selective inhibitors of these enzymes, thiorphan and captopril, respectively.…”

Section: Resultsmentioning

confidence: 99%

Degradation of the Alzheimer's Amyloid β Peptide by Endothelin-converting Enzyme

Eckman

Reed

Eckman

2001

Journal of Biological Chemistry

316

245

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Deposition of ␤-amyloid (A␤) peptides in the brain is an early and invariant feature of all forms of Alzheimer's disease. As with any secreted protein, the extracellular concentration of A␤ is determined not only by its production but also by its catabolism. A major focus of Alzheimer's research has been the elucidation of the mechanisms responsible for the generation of A␤. Much less, however, is known about the mechanisms responsible for A␤ removal in the brain. In this report, we describe the identification of endothelin-converting enzyme-1 (ECE-1) as a novel A␤-degrading enzyme. We show that treatment of endogenous ECE-expressing cell lines with the metalloprotease inhibitor phosphoramidon causes a 2-3-fold elevation in extracellular A␤ concentration that appears to be due to inhibition of intracellular A␤ degradation. Furthermore, we show that overexpression of ECE-1 in Chinese hamster ovary cells, which lack endogenous ECE activity, reduces extracellular A␤ concentration by up to 90% and that this effect is completely reversed by treatment of the cells with phosphoramidon. Finally, we show that recombinant soluble ECE-1 is capable of hydrolyzing synthetic A␤40 and A␤42 in vitro at multiple sites.

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“…The divergency of Ang-(1–12) metabolic pathways might be highly tissue specific, as a report suggested that neprilysin could also function as Ang-(1–12) convertase in the kidney [ 43 ]. Neprilysin is a major metalloproteinase member of the M13 family of proteases that also includes endothelin-converting enzyme (ECE) [ 44 ]. Since neprilysin activity in the kidney is very high compared to renal ACE activity [ 45• ], the data suggesting that neprilysin converts Ang-(1–12) into Ang I will need to be verified in studies in which more selective inhibitors of neprilysin are utilized.…”

Section: Ang-(1–12) Actions and Metabolismmentioning

confidence: 99%

Angiotensin-(1-12): A Chymase-Mediated Cellular Angiotensin II Substrate

et al. 2014

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The classical view of biochemical pathways for the formation of biologically active angiotensins continues to undergo significant revision as new data uncovers the existence of important species differences between humans and rodents. The discovery of two novel substrates that, cleaved from angiotensinogen, can lead to direct tissue angiotensin II formation has the potential of radically altering our understanding of how tissues source angiotensin II production and explain the relative lack of efficacy that characterizes the use of angiotensin converting enzyme inhibitors in cardiovascular disease. This review addresses the discovery of angiotensin-(1–12) as an endogenous substrate for the production of biologically active angiotensin peptides by a non-renin dependent mechanism and the revealing role of cardiac chymase as the angiotensin II convertase in the human heart. This new information provides a renewed argument for exploring the role of chymase inhibitors in the correction of cardiac arrhythmias and left ventricular systolic and diastolic dysfunction.

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Neprilysin II: A Putative Novel Metalloprotease and Its Isoforms in CNS and Testis

Cited by 49 publications

References 22 publications

Altered NEP2 Expression and Activity in Mild Cognitive Impairment and Alzheimer's Disease

Altered NEP2 Expression and Activity in Mild Cognitive Impairment and Alzheimer's Disease

Degradation of the Alzheimer's Amyloid β Peptide by Endothelin-converting Enzyme

Angiotensin-(1-12): A Chymase-Mediated Cellular Angiotensin II Substrate

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