ライフサイエンスコーパス: neprilysin

1 exhibited specificity for ECE-2 compared to neprilysin.

2 erting enzyme, insulin-degrading enzyme, and neprilysin.

3 lysin inhibitor, attenuated these effects of neprilysin.

4 ta (Abeta), and the Abeta-degrading protease neprilysin.

5 nhibit both the renin-angiotensin system and neprilysin.

6 substrate, and pathophysiological aspects of neprilysin.

7 ic peptides by inhibiting their breakdown by neprilysin.

8 arget, we used inducible drivers to modulate neprilysin 1 (Nep1) and dAbeta expression in adult DPM n

9 data reveal a functional interaction between neprilysin 1 and amyloid peptide, suggesting that nepril

10 lysin 1 and amyloid peptide, suggesting that neprilysin 1 degrades amyloid peptide.

11 we show that an increase in the level of the neprilysin 1 peptidase overcomes memory deficits induced

12 One gain was observed for the Neprilysin-1 (Nep1) gene, which has evolved a unique exp

13 Of particular interest is the NEP homolog neprilysin 2 (NEP2), which is thiorphan/phosphoramidon-s

14 tions, Abeta1-40 (20 muM) was incubated with neprilysin (300 ng/ml), an endopeptidase known to hydrol

15 opeptidase related in amino acid sequence to neprilysin, a mammalian cell-surface peptidase involved

16 is important to determine whether increased neprilysin activity also diminishes the levels of pathog

17 beta1 antagonist bisoprolol inhibited renal neprilysin activity and increased circulation NP levels

18 explore whether substances that can elevate neprilysin activity could be a rational option for treat

19 ed that RF-RDN significantly inhibited renal neprilysin activity in SHR and WKY with HF.

20 Islet neprilysin activity was inhibited or up-regulated using

21 l nerves on kidney function attenuates renal neprilysin activity, augments circulating NP levels, red

22 is mediated, at least in part, by decreased neprilysin activity.

23 ion of insulin-like peptides is regulated by neprilysin activity.

24 al development, was found to also target the neprilysin, aminopeptidase, and dipeptidylpeptidase clan

25 Now we studied the effect of neprilysin, an Abeta-degrading enzyme, on development of

26 We sought to determine whether neprilysin, an amyloid-degrading enzyme, is present in i

27 ding enzyme, endothelin-converting enzyme-1, neprilysin and alpha-secretase.

28 ning proved that Phe(3) is a key residue for neprilysin and aminopeptidase N (AP-N) ectoenkephalinase

29 wo of the three angiotensin-forming enzymes (neprilysin and endopeptidase 24.15) also contribute to t

30 Angiotensin-converting enzyme, neprilysin and endothelin-converting enzyme function as

31 in strongly decreased tissue availability of neprilysin and impaired enzymatic activity.

32 and spatial relationships between decreased neprilysin and increased cell growth.

33 m roles for endothelin-converting enzyme and neprilysin and indicate that reductions in these enzymes

34 tein, and its degradation by enzymes such as neprilysin and insulin degrading enzyme.

35 t was independent of mRNA/protein changes in neprilysin and insulin-degrading enzyme and, instead, ma

36 closely similar sites as wild-type Abeta by neprilysin and insulin-degrading enzyme, the two most wi

37 dation of Abeta peptides within microglia by neprilysin and related enzymes is dramatically enhanced

38 s revealed a global myocardial response, and neprilysin and the STAT family as key regulators of intr

39 pted us to search for an interaction between neprilysins and Drosophila Abeta (dAbeta), a cleavage pr

40 The high functional conservation of neprilysins and their substrates renders the characteriz

41 three enzymes: neutral endopeptidases 24.11 (neprilysin) and 24.15 and prolyl-endopeptidase 24.26.

42 by isolation of the enzyme that degrades it (neprilysin) and its inhibitors.

43 I and Ang-(1-7), together with cardiac ACE2, neprilysin, Ang II type 1 receptor (AT1), and mas recept

44 there has been no direct demonstration that neprilysin antagonizes the deposition of amyloid-beta in

45 Neprilysins are also required in the MB, reflecting the

46 gical target for Nep1.SIGNIFICANCE STATEMENT Neprilysins are endopeptidases known to degrade a number

47 Neprilysins are endopeptidases known to degrade a number

48 use Drosophila melanogaster to study whether neprilysins are involved in memory.

49 RNA interference, we show here that all four neprilysins are involved in middle-term and long-term me

50 Neprilysins are Type II metalloproteinases known to degr

51 Neprilysins are type II metalloproteinases known to degr

52 Finally, we provide evidence about soluble neprilysin as a biomarker surrogate in patients with hea

53 We next highlight the value of neprilysin as a biotarget and weigh the clinical benefit

54 suggest that the recombinant brain-targeted neprilysin, ASN12, may be an effective treatment for AD

55 an increase in the Abeta-degrading protease neprilysin at the cell surface and a concomitant increas

56 (2, 4-dinitrophenyl) is also a substrate for neprilysin, but is hydrolyzed 10-fold more efficiently b

57 Treatment with recombinant neprilysin, but not enzymatically inactive neprilysin, r

58 nificant regional association with BACE1 and neprilysin, but not PSD95 that regionally associated wit

59 genetically engineered form of the protease neprilysin completely arrest amyloid deposition in an ag

60 Median neprilysin concentration in 1,069 patients was 0.642 ng/

61 In age-adjusted Cox regression analyses, neprilysin concentrations were significantly associated

62 Neprilysin contributes to free fatty acid (FFA)-induced

63 This finding suggests that neprilysin could facilitate neuroreplacement therapy wit

64 In summary, neprilysin decreases islet amyloid deposition by inhibit

65 proves learning and memory deficits, whereas neprilysin deficiency aggravates the behavioral phenotyp

66 ely, angiotensin-(1-2) enhanced GSIS in both neprilysin-deficient and wild-type islets.

67 In neprilysin-deficient mouse islets, angiotensin-(1-7) and

68 under nonpathological conditions, mammalian neprilysins degrade amyloid peptide to ensure memory for

69 er, a more widely expressed islet peptidase, neprilysin, degrades angiotensin-(1-7) into several pept

70 at the mechanism for protection conferred by neprilysin deletion involves prevention of reduced calci

71 lysin on plaques and oligomers suggests that neprilysin-dependent degradation of Abeta affects plaque

72 proach to test the alternate hypothesis that neprilysin depletion increases chronic hypoxic pulmonary

73 eficient mouse islets, angiotensin-(1-7) and neprilysin-derived degradation products angiotensin-(1-4

74 odel of ECE-2 using the crystal structure of neprilysin (EC 3.4.24.11) as a template.

75 The fly genome contains five neprilysin-encoding genes, four of which are expressed i

76 In Drosophila, several neprilysins expressed in the brain are required for midd

77 We previously showed that all four neprilysins expressed in the Drosophila brain are involv

78 Functional studies involving neprilysin-expressing vascular endothelial cells demonst

79 Concomitant phenotypes of altered neprilysin expression included impaired food intake, red

80 CG4721 encodes a neprilysin family metalloprotease that is highly up-regu

81 Kell is classified in the neprilysin family of zinc endopeptidases, and XK has str

82 re not conserved in the other members of the neprilysin family, and based on the hypothesis that one

83 nase CD10/neutral endopeptidase 24.11 ([NEP] neprilysin) functions as part of a regulatory loop to co

84 Four neprilysin genes are expressed in adult Drosophila Using

85 Loss of neprilysin had no effect on baseline airway or alveolar

86 The endopeptidase neprilysin has been successfully used to reduce the accu

87 Neprilysin has recently been implicated as a major extra

88 apparent structural similarities, ECE-1 and neprilysin have been considered to differ significantly

89 drug classes, namely inhibitors of DPP IV or neprilysin, have been developed.

90 A screen for corresponding substrates of the neprilysin identified distinct peptides that regulate in

91 pinephrine, angiotensin II, aldosterone, and neprilysin) impair insulin sensitivity and contribute to

92 utations in MME encoding the metalloprotease neprilysin in 19 index case subjects diagnosed with axon

93 o assess the presence of circulating soluble neprilysin in a real-life cohort of HF patients and corr

94 d cardiomyocytes confirmed the importance of neprilysin in ameliorating PAO accumulation.

95 und zinc-metallopeptidase that is related to neprilysin in amino acid sequence.

96 ion of STAT1 and CASP3 and downregulation of neprilysin in both zones, suggesting r-I/R induced intri

97 Overexpression of the Abeta-degrading enzyme neprilysin in brains of human amyloid precursor protein

98 n beta-secretase activity and a reduction of neprilysin in female mice compared to males; this sugges

99 Identification of circulating neprilysin in HF patients and the positive association o

100 findings suggest that targeting the role of neprilysin in IAPP fibril assembly, in addition to IAPP

101 Importantly, adenoviral overexpression of neprilysin in islets cultured without FFA reproduces the

102 These data further support a role for neprilysin in regulating cerebral amyloid deposition and

103 suggesting the sustained elevation of islet neprilysin in these mice was a compensatory mechanism ai

104 Neprilysins in particular are the major amyloid-beta pep

105 Together, our data establish a role for neprilysins in two specific memory phases and further sh

106 rading enzymes (insulin-degrading enzyme and neprilysin) in APP/CCL2 and APP mice were indistinguisha

107 Neprilysin increased the number of neurospheres that for

108 romoting carcinogenesis, decreased levels of neprilysin increases inflammation and neuroendocrine cel

109 ss spectrometry, which failed to demonstrate neprilysin-induced cleavage.

110 and signaling, whereas exogenous recombinant neprilysin inhibited signaling.

111 Angiotensin receptor neprilysin inhibition (ARNI) therapy provided incrementa

112 These data suggest that neprilysin inhibition attenuates the risk of hyperkalemi

113 Angiotensin-neprilysin inhibition prevents the clinical progression

114 Following neprilysin inhibition, islet amyloid deposition and beta

115 chronic hypoxic pulmonary hypertension with neprilysin inhibition.

116 CZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), in patients with this disor

117 combined angiotensin receptor antagonist and neprilysin inhibitor addresses 2 of the pathophysiologic

118 The neprilysin inhibitor component of LCZ696, LBQ657, inhibi

119 We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angi

120 l size suggest that the angiotensin receptor neprilysin inhibitor LCZ696 may reduce this measure of m

121 NT) trial, in which the angiotensin receptor neprilysin inhibitor LCZ696 reduced markers of heart fai

122 We compared the angiotensin receptor-neprilysin inhibitor LCZ696 with enalapril in patients w

123 re (HF) treated with an angiotensin receptor neprilysin inhibitor lived longer without being hospital

124 cardiac hypertrophy than either stand-alone neprilysin inhibitor or angiotensin receptor blocker.

125 giotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio i

126 The angiotensin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696) reduc

127 The angiotensin receptor neprilysin inhibitor sacubitril/valsartan was associated

128 in Heart Failure), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan was more effec

129 d that a new angiotensin receptor antagonist-neprilysin inhibitor was superior to an angiotensin-conv

130 ospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With an Angiotensin-Converting Enzy

131 ospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin receptor blocker o

132 ive Comparison of ARNI (angiotensin-receptor-neprilysin inhibitor) with ACEI (angiotensin-converting

133 Phosphoramidon, a neprilysin inhibitor, attenuated these effects of nepril

134 alsartan, a combination angiotensin receptor-neprilysin inhibitor, improves morbidity and mortality i

135 bines an angiotensin receptor blocker with a neprilysin inhibitor, is well tolerated, and represents

136 ive Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] With ACEI [Angiotensin-Converting-

137 ive Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] with ACEI [Angiotensin-Converting-

138 ive Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] with ACEI [Angiotensin-Converting-

139 Angiotensin receptor neprilysin inhibitors (ARNi), beyond blocking angiotensi

140 antagonists (MRA), and angiotensin receptor-neprilysin inhibitors (ARNI), have not been studied in a

141 Combined angiotensin receptor blocker neprilysin inhibitors (ARNIs) have been associated with

142 rrent use of angiotensin-(1-7) compounds and neprilysin inhibitors as therapies for diabetes.

143 and weigh the clinical benefits of synthetic neprilysin inhibitors, either alone or in combination wi

144 cular pathways causing angioedema induced by neprilysin inhibitors, that is, sacubitril, are unclear,

145 nhibitors but insensitive to proteasomal and neprilysin inhibitors.

146 inical data from investigations of synthetic neprilysin inhibitors.

147 's disease (AD) markers, synaptophysin, APP, neprilysin, insulin-degrading enzyme and transthyretin i

148 including the endothelin-converting enzymes, neprilysin, insulin-degrading enzyme, and plasmin.

149 Neprilysin is a cell surface peptidase that catalyticall

150 Together, these findings demonstrate that neprilysin is a factor associated with islet amyloid acc

151 Neprilysin is a membrane-bound enzyme that breaks down n

152 Neprilysin is a metallopeptidase known to degrade amyloi

153 Neprilysin is a transmembrane metalloendopeptidase that

154 In sum, neprilysin is a versatile, veteran player returning yet

155 Neprilysin is a zinc-dependent endopeptidase.

156 ing live cell imaging, and that the protease neprilysin is involved in reduction of intraneuronal bet

157 Although neprilysin is known to degrade beta-amyloid, we observed

158 time that with prolonged FFA exposure, islet neprilysin is upregulated and this is associated with re

159 that require further research before soluble neprilysin is used clinically.

160 ctivity of an Abeta-degrading endopeptidase, neprilysin, is elevated in the brains of "enriched" mice

161 elevated in endothelin-converting enzyme and neprilysin knock-out mice, and inhibitors of these enzym

162 issue, a lentiviral vector expressing human neprilysin (Lenti-Nep) was tested in transgenic mouse mo

163 Associations between neprilysin level and a composite endpoint that included

164 Lung-targeted strategies to increase neprilysin levels could have therapeutic benefits in the

165 eal-life cohort of HF patients and correlate neprilysin levels with outcomes.

166 Rather, neprilysin may act by reducing hIAPP fibrillogenesis, wh

167 These data suggest that neprilysin may be protective against chronic hypoxic pul

168 l reduction of extracellular Abeta levels by neprilysin may facilitate development of HNPCs into neur

169 on and suggest that interventions to inhibit neprilysin may improve beta-cell function in obese human

170 To determine if neprilysin modulated amyloid deposition by cleaving hIAP

171 In contrast, neprilysin mRNA and activity did not decrease in amyloid

172 t in islets, including beta-cells, and islet neprilysin mRNA and activity were found to decline with

173 e of the treatments had an effect on cardiac neprilysin mRNA.

174 t AD is with Abeta-degrading enzymes such as neprilysin (NEP) and insulin-degrading enzyme (IDE).

175 ression and execution of two endopeptidases, neprilysin (NEP) and insulin-degrading enzyme.

176 Neprilysin (NEP) appears to be the most potent Abeta pep

177 mily of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important ques

178 ression of insulin-degrading enzyme (IDE) or neprilysin (NEP) in neurons significantly reduces brain

179 creased expression of Abeta-degrading enzyme neprilysin (NEP) in primary neuronal cultures.

180 an ethyl ester prodrug of LBQ657, the active neprilysin (NEP) inhibitor, and a component of LCZ696 (s

181 The endopeptidase neprilysin (NEP) is a major amyloid-beta (Abeta) degradi

182 Neprilysin (NEP) is a naturally occuring enzyme that bre

183 Neprilysin (NEP) is a zinc-dependent metalloprotease tha

184 Neprilysin (NEP) is an endopeptidase, which has an impor

185 s evidence that the Abeta-degrading protease neprilysin (NEP) is down-regulated in normal aging and L

186 Neprilysin (NEP) is one of the rate-limiting Abeta-degra

187 The Abeta-degrading enzyme neprilysin (NEP) is the best known target of these inhib

188 Neprilysin (NEP) is the dominant Abeta peptide-degrading

189 icrovessels and the Abeta-degrading protease neprilysin (NEP) occurred 14-21 d after a substantial de

190 abolism in kidney homogenates, we identified neprilysin (NEP) to be a major source of renal Ang-(1-7)

191 tein and mRNA for the Abeta-degrading enzyme neprilysin (NEP) was found, whereas various Abeta-cleari

192 Insulysin (IDE) and neprilysin (NEP) were found to be inactivated by oxidati

193 lin-derived peptides by proteases, including neprilysin (NEP).

194 The neprilysin (NEP)/endothelin-converting enzyme (ECE) fami

195 by two membrane-bound Zn-metallopeptidases, neprilysin (NEP, EC 3.4.24.11) and aminopeptidase N (APN

196 levels of the metallomembrane endopeptidase neprilysin, normal levels were maintained in the exercis

197 After chronic hypoxia, neprilysin-null mice exhibited exaggerated pulmonary hyp

198 Smooth muscle cells from neprilysin-null pulmonary arteries had increased prolife

199 This effect might result from degradation by neprilysin of endogenous Abeta produced and secreted by

200 The differential effect of neprilysin on plaques and oligomers suggests that nepril

201 re resistant to a 1-h incubation with either neprilysin or insulin degrading enzyme, whereas the mono

202 al cyclic guanosine monophosphate content by neprilysin or phosphodiesterase 9 inhibition, and myocar

203 In mouse models of Alzheimer's disease, neprilysin overexpression improves learning and memory d

204 Neprilysin overexpression reduced soluble Abeta levels b

205 ux and GSIS, suggesting that upregulation of neprilysin per se mediates insulin secretory dysfunction

206 s a substrate specificity similar to that of neprilysin, preferring to cleave substrates at the amino

207 These data indicate that neprilysin proteolytically inactivates fibroblast growth

208 hout exogenous Abeta1-40, the treatment with neprilysin reduced the number of developing colonies.

209 We previously showed that the enzyme neprilysin reduces islet amyloid deposition and thereby

210 omprehensive multivariable analyses, soluble neprilysin remained significantly associated with both t

211 mpared with controls, which was decreased by neprilysin replacement.

212 Neprilysin research has essentially focused on their rol

213 a specific inhibitor or adenovirus encoding neprilysin, respectively.

214 t neprilysin, but not enzymatically inactive neprilysin, resulted in a slight increase in basic fibro

215 Neprilysin's inability to prevent learning and memory de

216 To find out whether dAbeta was a neprilysin's target, we used inducible drivers to modula

217 Genetic ablation of neprilysin specifically protects against FFA-induced imp

218 e rapid, comparable with that of other known neprilysin substrates.

219 We previously characterized a recombinant neprilysin that contained a 38-amino acid brain-targetin

220 perineuronal net (PNN) and Mme encoding for Neprilysin, the enzyme degrading amyloid beta-peptides.

221 erted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation o

222 We previously demonstrated neprilysin to be present in pancreatic islets and now so

223 estion, we crossed hAPP transgenic mice with neprilysin transgenic mice and analyzed their offspring.

224 This effect of neprilysin was associated with reduced amounts of the mo

225 Circulating soluble neprilysin was measured with a modified sandwich immunoa

226 ving hIAPP, analysis of hIAPP incubated with neprilysin was performed by mass spectrometry, which fai

227 Neprilysin was present in islets, including beta-cells,

228 ed by 54 and 75%, respectively, whereas when neprilysin was up-regulated islet amyloid deposition and

229 ECE-1, unlike neprilysin, was found to have minimal activity against s

230 Neprilysin weakly but significantly correlated with age

231 rading enzymes, insulin degrading enzyme and neprilysin, were unchanged.

232 ding enzyme, the endogenous metallopeptidase neprilysin, which is fused to albumin to extend plasma h

233 HF patients and the positive association of neprilysin with cardiovascular mortality and morbidity f

234 not wild-type neurons show reduced levels of neprilysin with time in culture.