ライフサイエンスコーパス: HTRA1

1 proteins (e.g., MDK, NTN1, SMOC1, SLIT2, and HTRA1).

2 nst high-temperature requirement protein A1 (HtrA1).

3 e of human ovarian tumors with downregulated HtrA1.

4 ls, resulting in autocatalytic activation of HtrA1.

5 selectively cleaved by the human recombinant HTRA1.

6 ned medium with or without human recombinant HTRA1.

7 the alginate cultures overexpressing active HtrA1.

8 little is known about the function of human HtrA1.

9 ilial small vessel disease within NOTCH3 and HTRA1.

10 in limited autoproteolysis and activation of HtrA1.

11 cts serine protease activity associated with HtrA1.

12 2R, THSD7A, NELL1, PCDH7, NCAM1, SEMA3B, and HTRA1.

13 ta1 signalling through the secreted protease HTRA1.

14 tage of cells expressing the serine protease HtrA1.

15 cytoplasmic high temperature requirement A1 (Htra1), a marker of cellular oxidative stress.

16 ed production of temperature requirement A1 (Htra1), a marker of oxidative stress.

17 We report here that HtrA1, a candidate tumor suppressor, is downregulated in

18 otide polymorphism in the promoter region of HTRA1, a serine protease gene on chromosome 10q26, is a

19 One of the up-regulated proteins, HtrA1, a serine protease, was detected at high levels in

20 Data suggest that risk variants at ARMS2/HTRA1 act as a strong catalyst of progression once early

21 biomarker provides important information on HtrA1 activity and pharmacological inhibition within the

22 Furthermore, HTRA1 mRNA and HTRA1 activity are up-regulated in response to elevated

23 a biomarker to demonstrate the inhibition of HtrA1 activity in patients with AMD who were treated wit

24 erve as robust pharmacodynamic biomarkers of HtrA1 activity.

25 f aggrecan by HtrA1 was strongly enhanced by HtrA1 agonists such as CPII, a C-terminal hexapeptide de

26 HumHtrA2 is also homologous to human HtrA1, also known as L56/HtrA, which is differentially e

27 o a cryptic pocket at the S1' site region of HTRA1 and abolish catalysis by stabilizing a non-compete

28 re we provide evidence that decidua-secreted HtrA1 and HtrA3 antagonize HtrA4-mediated trophoblast in

29 by HtrA1 or HtrA3 knockdown, supporting that HtrA1 and HtrA3 are crucial for trophoblast-decidual cel

30 Specifically, HtrA1 and HtrA3 expression is up-regulated under decidua

31 In contrast, both HtrA1 and HtrA3 have been shown to inhibit trophoblast i

32 We demonstrated that HtrA1 and HtrA3 interact with and degrade HtrA4 and ther

33 man disease since dysregulation of placental Htra1 and placental oxidative stress are features of pre

34 he interaction between ARMS2 and smoking and HTRA1 and smoking, after adjustment for CFH and age.

35 HTRA1 and the predicted LOC387715/ARMS2 gene were both t

36 61170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3), using TaqMan SNP genotyping

37 61170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3; P>0.35).

38 Although specific alleles for CFH, ARMS2, HTRA1, and C3 may predict the development of AMD, they d

39 NOTCH3, HTRA1, and COL4A1/2 pathogenic variants in monogenic str

40 ing mechanism for modulating the activity of HTRA1, and highlight the utility of CKP-based phage disp

41 SerpinE2 binds to HtrA1, and the HtrA1 protease triggers degradation of th

42 rmed for the genes CCR3, CFH, CX3CR1, ERCC6, HTRA1, and VEGF.

43 MD patients were strongly immunolabeled with HTRA1 antibody.

44 oteolysis and a reduced affinity for an anti-HtrA1 antibody.

45 ly expressed proteins (DEP) including ANXA3, HTRA1, APOE, CST3, and CLU, shared between the cortex, h

46 CFH, C3, C2, and ARMS2/HTRA1 are associated with large drusen and advanced AMD.

47 lternative complement pathway, and LOC387715/HtrA1 are the most consistent genetic risk factors for a

48 The significant associations in ARMS2 and HTRA1 are with polymorphisms in strong LD that confer vi

49 ne hydrolase high-temperature requirement 1 (HTRA1) are associated with increased risk of age-related

50 e polymorphisms (SNPs) at the CFH, FZD4, and HTRA1/ARMS2 loci were tested for replication.

51 The SNP rs10490924 in HTRA1/ARMS2 showed a borderline association with respons

52 hr) 1 (CFH Y402H variant) and on Chr10 (near HTRA1/ARMS2) contribute the most risk.

53 These observations raise the possibility of HtrA1 as a candidate tumor suppressor involved in promot

54 h cartilage from healthy joints, implicating HtrA1 as a critical protease involved in proteoglycan tu

55 We previously identified serine protease HtrA1 as a downregulated gene in epithelial ovarian canc

56 results offer an original identification of HtrA1 as a microtubule-associated protein and provide in

57 The potential role of HtrA1 as a predictive factor of clinical response to che

58 We have previously identified HTRA1 as being up-regulated in osteoarthritic patients a

59 This activity is specific to HtrA1, as similar assays with HtrA2 showed minimal ApoE4

60 D risk region contains a long non-coding RNA HTRA1-AS1 (ENSG00000285955/BX842242.1) which colocalizes

61 HTRA1-AS1 has a strong retinal eQTL signal, pinpointing

62 Purified HtrA1 associates with purified alpha- and beta-tubulins,

63 Downregulation of HtrA1 attenuated cisplatin- and paclitaxel-induced cytot

64 Here, we report that loss of HtrA1 attenuates anoikis--a critical physiologic barrier

65 ell motility, whereas enhanced expression of HtrA1 attenuates cell motility.

66 HtrA1 augmentation, not inhibition, in high-risk patient

67 established that, like the human orthologue HtrA1, BbHtrA is proteolytically active against numerous

68 HtrA1 belongs to a family of serine proteases found in o

69 In this study, we have developed an HtrA1-blocking Fab fragment to test the therapeutic hypo

70 patients with AMD who were treated with the HtrA1-blocking Fab fragment.

71 and FTIR assays, we investigated the role of HtrA1 both in normal TGFBIp turnover and in corneal amyl

72 expression of a catalytically active form of HtrA1, but not an active site mutant (S328A), caused a m

73 cribe the allosteric inhibition mechanism of HTRA1 by a clinical Fab fragment, currently being evalua

74 he presence of risk alleles for CFH, ARMS 2, HTRA1, C3, or TLR3.

75 We show that HtrA1 can cleave WT TGFBIp but prefers amyloidogenic var

76 Mechanistically, HTRA1 carried by tumor-derived small extracellular vesic

77 dementia risk (OR, 5.42; 95% CI, 3.11-8.74), HTRA1 carriers an increased all-cause dementia risk (OR,

78 ted with increased stroke risk in NOTCH3 and HTRA1 carriers.

79 utations in the homotrimeric serine protease HTRA1 cause cerebral vasculopathy.

80 leotide polymorphisms in 7 genes (CFH, ARMS2/HTRA1, CFB, C2, C3, CFI, and LIPC) were genotyped.

81 Moreover, HtrA1 cleavage of the mutant FAS1-4 domains generated pe

82 pitope sequence (VQTV(356)) generated at the HtrA1 cleavage site was developed.

83 Recombinant HTRA1 cleaves RPE-secreted proteins involved in regulati

84 We show here that HtrA1 cleaves the WT FAS1-4 domain only inefficiently, w

85 for Mendelian small vessel disease: NOTCH3, HTRA1, COL4A1, COL4A2 and TREX1.

86 ture requirement A serine peptidase 1 (ARMS2/HTRA1), complement component 2 (C2), complement factor B

87 These findings suggest a link between HTRA1, complement regulation, and amyloid deposition in

88 Moreover, HtrA1 cosediments and copurifies with microtubules.

89 protease concentrations, is prevented under HtrA1-deficient conditions as well as by CARASIL mutatio

90 Bacterial HtrA1 (DegP) is a heat shock-induced protein that behave

91 We show here that human HTRA1 degrades aggregated and fibrillar tau, a protein t

92 The PDZ serine protease HTRA1 degrades fibrillar tau, which is associated with A

93 Finally, HTRA1 detoxifies alpha-syn fibrils and prevents formatio

94 Further, HTRA1 disaggregates preformed alpha-syn fibrils, renderi

95 In vitro, the R227W mutant HTRA1 efficiently proteolyzed the disordered substrate c

96 HTRA1 encodes a secreted serine protease implicated in f

97 ced cytotoxicity, while forced expression of HtrA1 enhanced cisplatin- and paclitaxel-induced cytotox

98 nnot be used to determine how abnormal ARMS2/HTRA1 expression can initiate RPE pathology.

99 mplete absence or markedly reduced levels of HtrA1 expression compared to the brushings of ovarian su

100 HTRA1 expression in genotyped RPE cells was determined b

101 tion of endogenous alpha-syn, while reducing HTRA1 expression promotes alpha-syn seeding.

102 HtrA1 expression was upregulated by both cisplatin and p

103 In response to loss of anchorage, HtrA1 expression was upregulated in SKOV3 cells, resulti

104 ate compared with those with lower levels of HtrA1 expression.

105 The cryo-EM structure of the HTRA1:Fab complex in combination with molecular dynamics

106 cell death, whereas protease-inactive mutant HtrA1 failed to result in either the inhibition of EGFR/

107 EXT1 and EXT2, NELL1, SEMA3B, NCAM1, CNTN1, HTRA1, FAT1, PCDH7, NTNG1, PCSK6 and NDNF, accounting fo

108 study, the authors focused on a substrate of HTRA1, fibronectin, because fibronectin fragments (Fnfs)

109 ng missense and loss-of-function variants in HTRA1 (frequency of 1 in 275 in the UK Biobank populatio

110 ing identified a recurrent in-frame SH3PXD2A-HTRA1 fusion in 12/125 (10%) cases, and genomic analysis

111 Expression of the SH3PXD2A-HTRA1 fusion resulted in elevated phosphorylated ERK, in

112 The HTRA1 gene encodes a secreted serine protease.

113 e polymorphism in the promoter region of the HTRA1 gene, as has previously been suggested.

114 Western blot analysis demonstrated that HtrA1-generated aggrecan fragments containing the VQTV(3

115 ith polymorphisms in the LOC387715/ARMS2 and HTRA1 genes on 10q26.

116 linked genome-wide association studies ARMS2/HTRA1 genes, located at the chromosome 10q26 locus, are

117 ified CFH, C2, C3, CFB, CFI, APOE, and ARMS2/HTRA1 genes/regions and the novel genes LIPC, CETP, and

118 emperature requirement A serine peptidase 1 (HTRA1) genes, as the strongest genetic risk factor for a

119 es not mediate the association between ARMS2/HTRA1 genotype and faster enlargement.

120 Reticular pseudodrusen presence and ARMS2/HTRA1 genotype are relatively independent risk factors,

121 ARMS2/HTRA1 genotype is more important in increasing risk of p

122 HtrA1 has also been reported to cleave the tau protein (

123 HTRA1 has the capacity to degrade numerous extracellular

124 Carriers of the risk haplotype at ARMS2/HTRA1 have a particularly high risk of late AMD at a rel

125 s sequence homology to human serine protease HtrA1 (hHtrA1).

126 MD, including two donors with the rare ARMS2/HTRA1 homozygous genotype.

127 sk of incident GA among those with the ARMS2/HTRA1 homozygous risk genotype (hazard ratio [HR] Q5 vs

128 2 (age-related maculopathy susceptibility 2)-HTRA1 (HtrA serine peptidase 1) (P =2.7 x 10(-72)), CFH

129 Mtb) has three putative HtrA-like proteases, HtrA1, HtrA2, and HtrA3.

130 the predicted tumor stroma-specific markers HTRA1, HTRA3, MXRA5, MXRA8, and SERPING1 in situ.

131 ons revealed that Fab binding to LoopA locks HTRA1 in a non-competent conformational state, incapable

132 To define the role of the serine protease HTRA1 in age-related macular degeneration (AMD) by exami

133 However, the precise role of HTRA1 in AMD remains elusive.

134 ether, these findings support a key role for HTRA1 in AMD susceptibility and identify a potential new

135 ), but the functional consequence of loss of HtrA1 in EOC remains largely unclear.

136 blood expression quantitative trait loci of HTRA1 in linkage disequilibrium.

137 By transgenically expressing human HTRA1 in mouse retinal pigment epithelium, we showed tha

138 s in our understanding of the role played by HTRA1 in musculoskeletal pathology.

139 However, the function of HTRA1 in other closely related musculoskeletal diseases

140 endent growth, while exogenous expression of HtrA1 in OV202 induces cell death.

141 nduced cytotoxicity and suggest that loss of HtrA1 in ovarian and gastric cancers may contribute to i

142 diated cell death and that downregulation of HtrA1 in ovarian cancer may contribute to malignant phen

143 eveal for the first time a novel function of HtrA1 in promoting anoikis by attenuating activation of

144 Stable knockdown of HtrA1 in SKOV3 and TOV21G cells resulted in resistance t

145 Downregulation of HtrA1 in SKOV3 by antisense transfection promotes anchor

146 skin fibroblasts for a facilitating role of HtrA1 in TGF-beta pathway activation.

147 sion, but the precise biological function of HtrA1 in the eye and its contribution to disease etiolog

148 d these studies and investigated the role of HTRA1 in the pathogenesis of intervertebral disc (IVD) d

149 now exist to support a detrimental role for HTRA1 in the pathogenesis of joint and intervertebral di

150 nitial mechanistic insights into the role of HtrA1 in the regulation of cell motility by modulating m

151 pigment epithelium, we showed that increased HTRA1 induced cardinal features of PCV, including branch

152 Recombinant HTRA1 induced MMP production in IVD cell cultures throug

153 HtrA1-induced cell death is not inhibited by the broad c

154 HTRA1-induced fibronectin proteolysis resulted in the ge

155 Active HtrA1 induces cell death in a serine protease-dependent

156 uspended SKOV3 cells, enhanced expression of HtrA1 inhibited EGFR/AKT pathway, leading to increased c

157 HTRA1 inhibition may preserve retinal integrity and slow

158 Here, we report that HTRA1 inhibits aggregation of alpha-syn as well as FUS a

159 and immunofluorescence assays revealed that HtrA1 interacted with EGFR not only on the cell membrane

160 d deposits in vivo, supporting the idea that HtrA1 is a causative agent for TGFBIp-associated amyloid

161 Human HTRA1 is a highly conserved secreted serine protease tha

162 ere, we report the first evidence that human HtrA1 is a microtubule-associated protein and modulates

163 Our data indicate that placentally expressed HTRA1 is a serine protease that cleaves A1AT in utero to

164 te that the widely conserved serine protease HTRA1 is activated by tau fibrils, providing quantitativ

165 ound in the nervous system, demonstrate that HtrA1 is an allele-selective ApoE-degrading enzyme that

166 Expression of HtrA1 is downregulated in five of seven ovarian cancer c

167 ion of its amyloid fibrils, a task that free HTRA1 is efficiently performing.

168 es, and neuritic plaques, respectively, when HTRA1 is expressed at elevated levels.

169 Intracellular HtrA1 is localized to microtubules in a PDZ (PSD95, Dlg,

170 These data suggest that HTRA1 is performing regulated proteolysis during protein

171 Our results indicate that increased HTRA1 is sufficient to cause PCV and is a significant ri

172 phism, rs11200638, in the promoter region of HTRA1 is the most likely causal variant for AMD at 10q26

173 High temperature requirement protein A1 (HtrA1) is a primarily secreted serine protease involved

174 ase high-temperature requirement protein A1 (HtrA1) is associated with protein-misfolding disorders s

175 -temperature requirement serine protease A1 (HTRA1) is one of four known proteases belonging to the b

176 based on the methylation of 3 genes (CACNB2, HTRA1, KLF4) identified a poorer-outcome patient subset.

177 By GD18, placental bed IL-18 and Htra1 levels, and uNK cell numbers were equivalent in co

178 ors, which are most exaggerated in the ARMS2/HTRA1 lines.

179 polysaccharide-stimulated PMNs isolated from HTRA1+/+ littermate control pups exhibit delayed NET for

180 competent earlier after birth compared with HTRA1+/+ littermate controls.

181 In contrast to bacterial HtrA1, little is known about the function of human HtrA1

182 nd a locus on chromosome 10 encompassing the HTRA1/LOC387715/ARMS2 genes.

183 f genetic variation at the CFH and LOC387715/HTRA1 loci and smoking, the effect remained significant

184 ficant association was observed at the ARMS2/HTRA1 locus (rs10490924; odds ratio [OR], 1.47; P = 4.3

185 f genetic risk, in addition to the LOC387715/HTRA1 locus and other environmental influences.

186 analysis and replication analysis, the ARMS2/HTRA1 locus confers increased risk for both advanced AMD

187 of an allele at microsatellite markers near htrA1 locus on 10q26.

188 eatures for rs3750486 genotypes at the ARMS2/HTRA1 locus were determined by logistic regression and w

189 ssociation of the rs3750846 SNP at the ARMS2/HTRA1 locus with subretinal/sub-retinal pigment epitheli

190 The association of the SNP at the ARMS2/HTRA1 locus with subretinal/sub-RPE hemorrhage and poore

191 Moreover, grafting the HTRA1-LoopA epitope onto HTRA2 and HTRA3 transferred the

192 ants, both chromosomes 1 (CFH) and 10 (ARMS2/HTRA1) major AMD risk loci are reidentified.

193 Our findings suggest that HTRA1 may be a therapeutic target for a range of neurode

194 on of TGF-beta signaling caused by a lack of HtrA1-mediated LTBP-1 processing as mechanism underlying

195 s in the gene encoding TGFBIp cause aberrant HtrA1-mediated processing that results in amyloidogenesi

196 be a novel pathway by which serine protease HtrA1 mediates paclitaxel- and cisplatin-induced cytotox

197 Here, we show that HTRA1 messenger RNA (mRNA) is reduced in retinal pigment

198 Senescent HTRA1 mice developed occult CNV, which likely resulted f

199 In addition, HTRA1 mice displayed retinal pigment epithelium atrophy

200 of pro-invasive and pro-angiogenic mediators HTRA1, MMP1, FAM3C, PDGFA, and ADAM10.

201 we identify a peptidic ligand that activates HTRA1 monomers.

202 Furthermore, HTRA1 mRNA and HTRA1 activity are up-regulated in respon

203 ssociated with elevated expression levels of HTRA1 mRNA and protein.

204 activity in three different cell lines, and HTRA1 mRNA expression exhibits no significant change bet

205 HTRA1 mRNA expression was significantly elevated in dege

206 HTRA1 mRNA levels were threefold higher in primary RPE c

207 ukoencephalopathy (CADASIL) and heterozygous HTRA1 mutation-related cerebral small vessel disease (CS

208 ups including CADASIL (n = 24), heterozygous HTRA1 mutation-related CSVD (n = 9) and healthy controls

209 d education in both CADASIL and heterozygous HTRA1 mutation-related CSVD groups (beta = 0.458, P = 0.

210 s decreased in both CADASIL and heterozygous HTRA1 mutation-related CSVD patients (Bonferroni-correct

211 hereditary CSVD, especially in heterozygous HTRA1 mutation-related CSVD.

212 of GA among those with the homozygous ARMS2/HTRA1 nonrisk genotype (HR, 1.0; P = 0.90).

213 mmon variants in COL4A1 and rare variants in HTRA1, NOTCH3, COL4A1, and CST3 have been associated wit

214 h CFH-CFHR5 on chromosome 1 (Chr1) and ARMS2/HTRA1 on chromosome 10 (Chr10).

215 JAR cell invasion, which can be reversed by HtrA1 or HtrA3 knockdown, supporting that HtrA1 and HtrA

216 ess HtrA4-expressing JAR cell invasion in an HtrA1- or HtrA3-dependent manner.

217 -H3, DEL-1, vitronectin, and serine protease HtrA1 (P < 0.01).

218 at CFH (P = 6.0e-33) and rs61871744 at ARMS2-HTRA1 (P = 4.2e-20).

219 onstrate, by evaluating 45 tag SNPs spanning HTRA1, PLEKHA1, and predicted gene LOC387715/ARMS2, that

220 functional analyses, the disease-associated HTRA1 polymorphism resulted in a 2-fold increase in gene

221 rs11200638 SNP has no significant impact on HTRA1 promoter activity in three different cell lines, a

222 gher in primary RPE cells homozygous for the HTRA1 promoter risk allele than in RPE cells with the wi

223 A (homozygote risk) genotype at rs11200638 - HTRA1 promoter SNP (P = 0.001) and GG (homozygote risk)

224 The HTRA1 promoter SNP (rs11200638) and A69S at LOC387715/AR

225 emperature requirement A serine peptidase 1 (HTRA1) promoter.

226 Finally, downregulation of HtrA1 promotes cell motility, whereas enhanced expressio

227 esults therefore support a scenario in which HTRA1 promotes IVD degeneration through the proteolytic

228 In vitro, purified HtrA1 promotes microtubule assembly.

229 ed cell death, suggesting the requirement of HtrA1 protease activity in regulating anoikis.

230 ment to test the therapeutic hypothesis that HtrA1 protease activity is involved in the progression o

231 d that the presence of a rare variant in the HTRA1 protease domain corresponded to a larger effect th

232 standardized Phecodes, rare variants in the HTRA1 protease domain were associated with multiple neur

233 Similarly, overexpression of the HtrA1 protease impaired NC cell migration and the format

234 rtant role of rare genetic variation and the HTRA1 protease in determining WMH burden in the general

235 SerpinE2 HtrA1 protease Syndecan-4 -> NC cell migration.

236 SerpinE2 binds to HtrA1, and the HtrA1 protease triggers degradation of the cell surface

237 HtrA1 protein increases with age in the RPE-Bruch's memb

238 ssue extracts identified the serine protease HtrA1/PRSS11 as a major protein component of human artic

239 - pups had no detectable NIPs, and PMNs from HTRA1-/- pups became NET competent earlier after birth c

240 However, plasma from HTRA1-/- pups had no detectable NIPs, and PMNs from HTRA

241 Genetic experiments in Htra1(R274Q) mice further demonstrate that expression of

242 orrector in trans is sufficient to stabilize HtrA1-R274Q and restore the proteomic signature of the b

243 HTRA1 remodels alpha-syn fibrils by targeting the NAC do

244 ative or recombinant aggrecan with wild type HtrA1 resulted in distinct cleavage of these substrates.

245 ulins, and immunoprecipitation of endogenous HtrA1 results in coprecipitation of alpha-, beta-, and g

246 o two other HtrA proteases, E. coli DegP and HtrA1, revealed that all three HtrA proteases were rever

247 duals with late AMD, 64.7% carried the ARMS2/HTRA1 risk allele.

248 ARMS2/HTRA1 risk alleles decrease SOD2 defense, making RPE mor

249 s with RPD and in individuals carrying ARMS2/HTRA1 risk alleles.

250 donor eyes and screened for CFH, ARMS2, and HTRA1 risk genotypes by using an allele-discrimination a

251 l loci, 10 previously reported loci in ARMS2/HTRA1 (rs10490924), CFH (rs1061170, and rs1410996), CFB

252 ell death caused by ARMS2 rs10490924 but not HTRA1 rs11200638.

253 3766404, rs1061170, rs2274700 and rs393955), HTRA1 (rs11200638), CFHR1-5 (rs10922153, rs16840639, rs6

254 enotyping was performed for CFH (rs1061170), HTRA1 (rs1200638), and C3 (rs2230199).

255 associations of a common intronic variant in HTRA1, rs2293871 using single variant association testin

256 They reduced HtrA1's abilities to associate with IGF-1 and to amelior

257 translation rate and appeared to compromise HtrA1's conformation and function.

258 sociated synonymous polymorphisms lie within HtrA1's putative insulin-like growth factor 1 (IGF-1) bi

259 which translated into a twofold increase in HTRA1 secretion by RPE cells with the risk genotype.

260 nfirmed these effects to be primarily due to HTRA1 serine protease activity.

261 r gastric tumors expressing higher levels of HtrA1 showed a higher response rate compared with those

262 for complement, homozygous carriers of ARMS2/HTRA1 showed a higher risk of CNV (OR, 4.1; 95% CI, 3.2-

263 Most importantly, downregulation of HtrA1 significantly enhanced the peritoneal disseminatio

264 le nucleotide polymorphism (SNP) rs10490924, HTRA1 SNPs rs11200638 and rs3793917, and CFH SNPs rs3939

265 odels to elucidate the in vivo repertoire of HtrA1-specific substrates, and identified substrates tha

266 mary, our results indicate that TGFBIp is an HtrA1 substrate and that some mutations in the gene enco

267 , the identification of ApoE4 as an in vitro HtrA1 substrate suggests a potential biochemical mechani

268 sform this domain into a considerably better HTRA1 substrate.

269 Potential HTRA1 substrates were identified by incubating RPE-condi

270 One of these HtrA1 substrates, Dickkopf-related protein 3 (DKK3), was

271 A novel HtrA1-susceptible cleavage site within the interglobular

272 ator of TGF-beta bioavailability, as a novel HtrA1 target.

273 AMD) harbor synonymous SNPs within exon 1 of HTRA1 that convert common codons for Ala34 and Gly36 to

274 variants of high-temperature requirement A1 (HTRA1) that increase the inherited risk of neovascular a

275 ) genes (ARMS2, C3, C9, CD46, CFB, CFH, CFI, HTRA1, TIMP3, and SLC16A8), and 3 genes that cause inher

276 Our data highlight the potential of HTRA1 to act in a cell non-autonomous defense mechanism

277 unctional studies have shown a mechanism for HTRA1 to instigate ocular tissue abnormalities.

278 ve linked a multifunctional serine protease, HTRA1, to AMD.

279 in and was also found to be increased within HTRA1-treated IVD cell cultures as well as in disc tissu

280 rescued NC migration defects induced by both HtrA1 upregulation and SerpinE2 downregulation.

281 prototypical R274Q mutation, we identify an HTRA1 variant that promotes trimer formation thus restor

282 NOTCH3 and HTRA1 variants were associated with magnetic resonance i

283 cipants carried NOTCH3 variants, 546 carried HTRA1 variants, and 336 carried COL4A1/2 variants.

284 vage of chondroadherin at this site and that HTRA1 was indeed the only protease capable.

285 effect for both smoking with ARMS2 and with HTRA1 was not statistically significant.

286 A sustained pharmacodynamic effect of anti-HtrA1 was observed in the aqueous humor, as measured by

287 Cleavage of aggrecan by HtrA1 was strongly enhanced by HtrA1 agonists such as CP

288 igh-temperature requirement serine protease (HTRA1) was identified as a candidate age-related macular

289 FHTR2163, a novel Fab directed against HtrA1, was well tolerated with no DLTs or significant oc

290 CFH, C3, C2, and ARMS2/HTRA1 were associated with large drusen and advanced AMD

291 The genes CFH, C3, CFB, and ARMS2/HTRA1 were associated with progression from intermediate

292 ased protein levels of the processed form of HTRA1 were demonstrated in degenerate disc tissues via i

293 Both SGTB and HTRA1 were downregulated in the aorta of patients with c

294 Two SNPs in ARMS2 and HTRA1 were genotyped in 685 cases and 269 controls by a

295 ne variant within LOC387715/ARMS2 and one in HTRA1 were significantly associated with affected status

296 enoid lesions in rhesus monkeys in ARMS2 and HTRA1 were similar in frequency between the two phenotyp

297 temperature requirement serine peptidase A1 (HtrA1), which is found in the nervous system, demonstrat

298 Here we show that expression of HtrA1, which is frequently downregulated in ovarian canc

299 cluding Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious p

300 Inhibition of HtrA1 with a Fab did not slow down GA progression.

301 e microscopy demonstrates the interaction of HTRA1 with tau fibrils and their proteolytic degradation