ライフサイエンスコーパス: NPC1

1 the lipid transporter Niemann-Pick type C1 (NPC1).

2 helator and the only promising treatment for NPC1.

3 fered with the interaction between TIM-1 and NPC1.

4 When added to CHO cells, U-X crosslinked to NPC1.

5 entry also begins after colocalization with NPC1.

6 it has little impact on GP binding to mouse NPC1.

7 e hypothesized a role for these receptors in NPC1.

8 critical EBOV entry factors cathepsin B and NPC1.

9 ncreased lifespan in mouse and cat models of NPC1.

10 rotein that regulates the sterol transporter NPC1.

11 rial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems fro

12 Niemann-Pick C1 (NPC1), a membrane protein of lysosomes, is required for

13 sterol accumulation in neurons with impaired NPC1 activity.

14 ce to deplete Chinese hamster ovary cells of NPC1 alone or in combination with MLN64, which mediates

15 lation of the non-specific phospholipase C1, NPC1, alters silicon content in nodes and husks of rice

16 ciency (AATD), Niemann-Pick type C1 disease (NPC1), Alzheimer's disease (AD), and cystic fibrosis (CF

17 es of FTY720 to mice increased expression of NPC1 and -2 in brain and liver and decreased cholesterol

18 FTY720 greatly increased expression of NPC1 and -2 in human NPC1 mutant fibroblasts that correl

19 esent a 4.4 A structure of full-length human NPC1 and a low-resolution reconstruction of NPC1 in comp

20 proteins known to interact with cathepsin D, NPC1 and ABCA1.

21 The observation that Npc1 and Cstb deletion genetically interact to potently

22 A, a compound that has been shown to bind to NPC1 and inhibit cholesterol export.

23 ight the discovery of the lysosomal proteins NPC1 and LAMP1 as intracellular receptors for Ebola viru

24 FTY720/fingolimod increases NPC1 and NPC2 expression and reduces cholesterol and sph

25 d storage disease caused by mutations in the NPC1 and NPC2 genes.

26 Bronchoalveolar lavage from NPC1 and NPC2 mutant mice had an approx. 4-fold and 2.5-

27 Alveolar macrophages from the NPC1 and NPC2 mutant mice were enlarged compared to thos

28 ar body size, the lung phenotype seen in the NPC1 and NPC2 mutant mice were similar.

29 The lack of NPC1 and NPC2 proteins resulted in a disruption of the t

30 ta-hydroxyl group; they also bind tightly to NPC1 and NPC2 proteins that export cholesterol from lyso

31 type C (NPC) is associated with mutations in NPC1 and NPC2, whose gene products are key players in th

32 er of two late endosomal/lysosomal proteins, NPC1 and NPC2.

33 nists may represent a therapeutic option for NPC1 and provide insights on their mechanisms of action.

34 ells through endolysosomes that contain both NPC1 and TPC2.

35 d alleviated pathological phenotypes in both NPC1 and Wolman fibroblasts.

36 e integral membrane protein Niemann-Pick C1 (NPC1) and a soluble protein, Niemann-Pick C2 (NPC2).

37 del of the LSD Niemann-Pick type C1 disease (NPC1) and in a prospective 5-year international study of

38 as performed using both BALB/cJ and C57BL/6J Npc1+/+ and Npc1+/- mice to determine if decreased Npc1

39 ed growth studies using BALB/cJ Npc1 normal (Npc1+/+) and Npc1 heterozygous (Npc1+/-) mice and determ

40 teine proteases unmasks the binding site for NPC1, and GP-NPC1 engagement within lysosomes promotes a

41 otein Niemann-Pick disease type C protein 1 (NPC1) arising during early stages of viral infection.

42 Our work identifies NPC1 as a genetic determinant of filovirus susceptibilit

43 tion in EBOV entry and the attractiveness of NPC1 as an antifiloviral therapeutic target.

44 e that received a single dose of AAV9-CamKII-NPC1 as neonates (2.6 x 1011GC) or at weaning (1.3 x 101

45 Treatment with AAV9-EF1a-NPC1, as compared to AAV9-CamKII-NPC1, resulted in signi

46 -approved drug that has been shown to reduce NPC1-associated neuropathology.

47 ice that received a single dose of AAV9-EF1a-NPC1 at weaning (1.2 x 1012GC), exhibited an increased l

48 Proteolytic cleavage and NPC1 binding at endosomal pH lead to conformational rear

49 eduction of TMEM97, a cholesterol-responsive NPC1-binding protein, increases NPC1 levels in cells thr

50 This mutation, located at the NPC1-binding site on EBOV GP, occurred early in the 2013

51 The second luminal domain of NPC1 binds directly and specifically to the viral glycop

52 The discrimination between NPC1 (both miglustat treated and untreated) and healthy

53 inhibiting conformational changes in primed, NPC1-bound GP that initiate fusion between the viral and

54 tation in the sterol-sensing domain (SSD) of NPC1, but not by point mutation in the N-terminal domain

55 he F88A mutation impairs GP binding to human NPC1 by 10-fold, it has little impact on GP binding to m

56 tion of four autophagy related genes; DRAM1, NPC1, CASP3, and EIF2AK3/PERK.

57 respiratory chain), which is compromised in NPC1 cells.

58 ly inside cholesterol-rich late endosomes in Npc1(-/-) cells.

59 learance from endo/lysosomes of Npc1 mutant (Npc1(-/-)) cells.

60 We found that TIM-1 and NPC1 colocalized and interacted in the intracellular ves

61 ion and growth signaling through the SLC38A9-NPC1 complex.

62 ound signatures of positive selection in bat NPC1 concentrated at the virus-receptor interface, with

63 contrast, P-X cross-linking was reduced when NPC1 contained a point mutation (P691S) in its putative

64 NPC1 contains 13 transmembrane segments (TMs) and three

65 Antigen-pulsed NPC1(-/-) DCs are able to effectively activate antigen-s

66 tide binding to nascent MHC-II are normal in NPC1(-/-) DCs.

67 but the pathogenic mechanisms through which NPC1 deficiency causes neuronal dysfunction remain large

68 show that the clearance of autophagosomes in NPC1 deficiency is impaired due to inhibition of lysosom

69 C1-deficient cells and brain tissue and that NPC1 deficiency leads to alterations in mitochondrial fu

70 Here, we investigated the impact of NPC1 deficiency on rodent neurons using pharmacologic an

71 hingolipids is seen as a primary hallmark of NPC1 deficiency, our lipidomics analysis revealed the bu

72 defective lysosomal turnover resulting from NPC1 deficiency.

73 wild-type and Niemann-Pick disease type C1 (NPC1) deficient cells.

74 lesterol also accumulates in mitochondria of NPC1-deficient cells and brain tissue and that NPC1 defi

75 NPC1-deficient cells show enhanced cellular retention of

76 and restores normal lysosomal proteolysis in NPC1-deficient cells, supporting a model in which activa

77 ferase and stored in lipid droplets (LDs) in NPC1-deficient cells.

78 fic promoter regions of single-copy genes in NPC1-deficient cerebellum at early stages of the disease

79 lism in presymptomatic and early symptomatic NPC1-deficient cerebellum.

80 lesterol showed that lysosomes purified from NPC1-deficient fibroblasts contained at least 30% less c

81 t was significantly lower after treatment of NPC1-deficient human fibroblasts with benzyl-2-acetamido

82 In the absence of galactose supplementation, NPC1-deficient ldl-D cells also transported more cholest

83 CRISPR generated, NPC1-deficient ldl-D cells supplemented with galactose a

84 abnormal morphogenesis of the cerebellum of Npc1-deficient mice and show, for the first time, that t

85 igated amino acid metabolism in cerebella of NPC1-deficient mice at different stages of NPC disease.

86 Deletion of the encoding Cstb gene in Npc1-deficient mice resulted in striking deleterious eff

87 d ciliary proteins are severely disturbed in Npc1-deficient mice.

88 duction of the fraction of ciliated cells in Npc1-deficient mouse brains and the human fibroblasts of

89 f lysosomal cathepsins within the cytosol of Npc1-deficient Purkinje cells.

90 that the antigen processing compartments in NPC1(-/-) dendritic cells (DCs) have an abnormal ultrast

91 blasts and reduces cholesterol storage in an NPC1-dependent manner.

92 elevated mitochondrial cholesterol levels in NPC1-depleted cells and in NPC2-depleted cells expressin

93 prevented the increased lactate secretion in NPC1-depleted cells.

94 A murine model of NPC1 disease (Npc1-/-) displays a rapidly progressing fo

95 l mouse model faithfully recapitulates human NPC1 disease and provides a powerful tool for preclinica

96 reases in plasma 24(S)-HC in two independent NPC1 disease animal models, findings that were confirmed

97 duces lipid storage and prolongs survival in NPC1 disease animal models.

98 Whereas the prominent features of human NPC1 disease are replicated in the null Npc1(-/-) mouse,

99 s has been hypothesized to contribute to the NPC1 disease pathological cascade.

100 ts reducing oxidative stress could alleviate NPC1 disease phenotypes, the in vivo effects of the anti

101 acetylcysteine (NAC) on two mouse models for NPC1 disease were studied.

102 1-/-) displays a rapidly progressing form of NPC1 disease which is characterized by weight loss, atax

103 sing this approach, we were able to identify NPC1 disease with 91% accuracy confirming that there are

104 odel displays a less severe, delayed form of NPC1 disease with respect to weight loss, decreased moto

105 of NAC could provide potential treatment of NPC1 disease, possibly in concert with other therapeutic

106 l accelerate development of therapeutics for NPC1 disease.

107 new route to effective drug development for NPC1 disease.

108 le insight in to the underlying pathology of NPC1 disease.

109 ormation of the primary cilium is altered in NPC1 disease.

110 The Niemann-Pick type C1 (NPC1) disease is a neurodegenerative lysosomal storage d

111 Niemann-Pick type C1 (NPC1) disease is a rare autosomal recessive, neurodegene

112 Niemann-Pick type C1 (NPC1) disease is a rare neurovisceral disorder character

113 Niemann-Pick Type C1 (NPC1) disease is a rare neurovisceral, cholesterol-sphin

114 Niemann-Pick C1 (NPC1) disease is a rare, neurodegenerative lysosomal cho

115 xcipients can be used as admixtures to treat NPC1 disorder.

116 A murine model of NPC1 disease (Npc1-/-) displays a rapidly progressing form of NPC1 dis

117 Loss of NPC1 disrupts cholesterol trafficking from late endosome

118 Indeed, MR78 blocks binding of the essential NPC1 domain C.

119 SO mouse as an efficient model for candidate NPC1 drug screening, and demonstrated similarities in he

120 asm, without blocking trafficking of VLPs to NPC1(+) endolysosomes, where EBOV fuses.

121 es unmasks the binding site for NPC1, and GP-NPC1 engagement within lysosomes promotes a late step in

122 NPC1 patients and suggest that extraneuronal NPC1 expression can further augment the lifespan of the

123 es involved in cholesterol efflux (ABCA1 and NPC1), fatty acid metabolism (CROT and CPT1a), and insul

124 e A2AR agonist CGS21680 on human control and NPC1 fibroblasts.

125 Furthermore, although SARS does not require NPC1 for entry, SARS entry also begins after colocalizat

126 H, PPARD, CDK6, VPS13B, GAD2, GAB2, APOH and NPC1) for low-density lipoprotein cholesterol (LDL-C), a

127 nic mouse with liver-selective expression of NPC1 from embryonic stages.

128 generated neurons with decreased function of NPC1 from human embryonic stem cells and used them to te

129 NPC1 from rice hydrolyzed phospholipids and galactolipid

130 Human NPC1 fulfills a cardinal property of viral receptors: it

131 Therefore, decreased Npc1 gene dosage among two different mouse strains inter

132 (Npc1+/-) mice and determined that decreased Npc1 gene dosage interacts with a high-fat diet to promo

133 + and Npc1+/- mice to determine if decreased Npc1 gene dosage predisposes to metabolic features assoc

134 rus serotype 9 (AAV9) vectors to deliver the NPC1 gene under the transcriptional control of the neuro

135 mal storage disorder due to mutations in the NPC1 gene, encoding a transmembrane protein related to t

136 (NPC1), which arises from a mutation in the NPC1 gene, is characterized by abnormal cellular storage

137 caused by loss-of-function mutations in the NPC1 gene, is characterized by progressive neurodegenera

138 caused by loss-of-function mutations in the NPC1 gene.

139 The human Niemann-Pick C1 (NPC1) gene has been found to be associated with extreme

140 ur findings also highlight the importance of NPC1-GP interaction in EBOV entry and the attractiveness

141 mucin domain 1 (TIM-1) and Niemann-Pick C1 (NPC1) have been identified as attachment and fusion rece

142 M) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruse

143 Affected NPC1 patients and NPC1 heterozygote carriers had reduced NK-cell numbers i

144 dies using BALB/cJ Npc1 normal (Npc1+/+) and Npc1 heterozygous (Npc1+/-) mice and determined that dec

145 ctive of the present study was to develop an NPC1 I1061T knock-in mouse in which to test proteostatic

146 gonists increased steady-state levels of the NPC1 I1061T protein.

147 The murine NPC1(I1061T) protein has a reduced half-life in vivo, co

148 The most prevalent mutation, NPC1(I1061T), encodes a misfolded protein with a reduced

149 el is that cells will be less dependent upon NPC1 if their glycocalyx is decreased in density.

150 NPC1 and a low-resolution reconstruction of NPC1 in complex with the cleaved glycoprotein (GPcl) of

151 of TMEM97 also increases levels of residual NPC1 in NPC1-mutant patient fibroblasts and reduces chol

152 these studies suggest an important role for NPC1 in the differential entry of GP-F88A into mouse ver

153 We found that the depletion of NPC1 increased lactate secretion, decreased glutamine-de

154 In parallel, beta-cyclodextrin mediated the NPC1-independent redistribution of cholesterol within ne

155 , which greatly reduces the affinity of EBOV-NPC1 interaction.

156 Here, we demonstrate that NPC1 is a critical filovirus receptor.

157 NPC1 is also the intracellular receptor for Ebola virus

158 NPC1 is essential for transporting cholesterol and other

159 sting that the interaction between TIM-1 and NPC1 is important for filovirus membrane fusion.

160 Finally, ectopic expression of NPC1 is sufficient to rescue entry into an undifferentia

161 NPC1 is the first known viral receptor that recognizes i

162 Niemann-Pick type C1 disease (NPC1) is a fatal genetic disorder caused by impaired int

163 Niemann-Pick disease, type C1 (NPC1) is a heritable lysosomal storage disease character

164 Niemann-Pick type C1 (NPC1) is a late endosomal transmembrane protein, which,

165 Niemann-Pick C1 (NPC1) is a lysosomal membrane protein that exports chole

166 Niemann-Pick disease, type C1 (NPC1) is a lysosomal storage disorder characterised by p

167 Niemann-Pick type C1 (NPC1) is shown to be an important regulator of the major

168 ays distinct from those initially altered by Npc1 knockdown, data consistent with NAC achieving parti

169 th antisense-induced (NPC1ASO) and germline (Npc1-/-) knockout genetic mouse models, confirming the p

170 s in selectively late endosomes/lysosomes of NPC1-KO cells.

171 ctivity, we tested and provide evidence that NPC1(+) LE/Lys have higher cathepsin L activity than LE,

172 an unexplored vulnerability, trafficking to NPC1(+) LE/Lys, as a therapeutic target for SARS and EBO

173 traffic late into the endocytic pathway, to NPC1(+) LE/Lys, in order to enter host cells, and that t

174 In TMEM97 knockdown cells, NPC1 levels can be reinstated with wild type TMEM97, but

175 ion as a novel strategy to increase residual NPC1 levels in cells and a potential therapeutic target

176 l-responsive NPC1-binding protein, increases NPC1 levels in cells through a post-transcriptional mech

177 scription (RT)-PCR assays demonstrate higher NPC1 levels in GP-F88A permissive IC-21 cells and mouse

178 t framework for mechanistic understanding of NPC1-mediated intracellular cholesterol trafficking and

179 NK cells from NPC1 mice also had a defect in cytotoxicity due to a fai

180 that administration of cyclodextrin (CD) to Npc1(-/-) mice eliminates cholesterol sequestration in L

181 ic CD4 T cells in vitro, and immunization of NPC1(-/-) mice reveals surprisingly normal CD4 T cell ac

182 ary cultures of neurons and glial cells from Npc1(-/-) mice were incubated for 24 h with 0.1 to 10 mm

183 f C57BL/6J Npc1+/- mice compared to C57BL/6J Npc1+/+ mice.

184 ut not in the adipose or muscle, of C57BL/6J Npc1+/- mice compared to C57BL/6J Npc1+/+ mice.

185 using both BALB/cJ and C57BL/6J Npc1+/+ and Npc1+/- mice to determine if decreased Npc1 gene dosage

186 The results indicated that C57BL/6J Npc1+/- mice, but not BALB/cJ Npc1+/- mice, have impaire

187 that C57BL/6J Npc1+/- mice, but not BALB/cJ Npc1+/- mice, have impaired glucose tolerance when fed a

188 Npc1 normal (Npc1+/+) and Npc1 heterozygous (Npc1+/-) mice and determined that decreased Npc1 gene do

189 sion can further augment the lifespan of the Npc1-/- mice after systemic AAV gene delivery.

190 euron precursors is significantly reduced in Npc1-/- mice due to the downregulation of Shh expression

191 The Npc1-/- mice that received a single dose of AAV9-CamKII-

192 n the central nervous system of AAV9 treated Npc1-/- mice.

193 19 and NS11021 in a number of LSDs including NPC1, mild cases of mucolipidosis type IV (ML4) (TRPML1-

194 tion crystal structure of a complex of human NPC1-MLD and NPC2 bearing bound cholesterol-3-O-sulfate.

195 NPC1-MLD uses two protruding loops to bind NPC2, analogo

196 expression patterns between the NPC1ASO and Npc1-/- models.

197 These data indicate that NPC1 modulates silicon distribution and secondary cell w

198 A trimeric EBOV-GPcl binds to one NPC1 monomer through the domain C.

199 cterized liver gene expression changes in an Npc1 mouse model at six ages spanning the pathological p

200 In an NPC1 mouse model, we found the frequency of NK cells was

201 velopmental changes to those observed in the NPC1 mouse.

202 uman NPC1 disease are replicated in the null Npc1(-/-) mouse, this model is not amenable to examining

203 Compared with the Npc1(-/-) mouse, this Npc1(tm(I1061T)Dso) model displays

204 Although Npc1 mRNA levels appear relatively normal, Npc1(nmf164)

205 cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1(-/-)) cells.

206 Pulmonary features of NPC1 mutant felines reflected the disease described in N

207 h this finding, FTY720 pretreatment of human NPC1 mutant fibroblasts restored transport of the choler

208 increased expression of NPC1 and -2 in human NPC1 mutant fibroblasts that correlated with formation o

209 ingolipid storage and trafficking defects in NPC1 mutant fibroblasts.

210 components of the surfactant system in both NPC1 mutant mice and felines and in NPC2 mutant mice nea

211 t felines reflected the disease described in NPC1 mutant mice.

212 rescues the cholesterol storage phenotype in NPC1-mutant fibroblasts.

213 97 also increases levels of residual NPC1 in NPC1-mutant patient fibroblasts and reduces cholesterol

214 At the level of electron microscopy, NPC1-mutant type II cells had uncharacteristically large

215 management of patients with loss-of-function NPC1 mutations.

216 d in which ebolavirus enters through a later NPC1-negative endosome that contains two-pore Ca(2+) cha

217 tion is an exceptionally severe phenotype in NPC1 neurons compared with fibroblasts, causing abnormal

218 We found that human NPC1 neurons have strong spontaneous activation of autop

219 These studies in Npc1(-/-) neurons and astrocytes establish a dose of CD

220 kinje cell loss at a slower rate than in the Npc1(nih) mouse model.

221 h Npc1 mRNA levels appear relatively normal, Npc1(nmf164) brain and liver display dramatic reductions

222 severe infantile onset forms of NPC disease, Npc1(nmf164) mice offer many advantages as a model for t

223 ously performed growth studies using BALB/cJ Npc1 normal (Npc1+/+) and Npc1 heterozygous (Npc1+/-) mi

224 Docking of the NPC1-NPC2 complex onto the full-length NPC1 structure re

225 Although NPC1/NPC2 constitutes the major pathway, therapies that

226 ation of a diverse set of glycoconjugates in NPC1-null and NPC2-deficient fibroblasts within endocyti

227 and progression of neurodegeneration of the NPC1-null animal.

228 Treatment of either NPC1-null or NPC2-deficient cells with cyclodextrin was

229 In addition, the node cells of NPC1-OE plants have lower contents of cellulose and hemi

230 resulted in the opposite changes to those of NPC1-OE plants.

231 e defects in the endosomal-lysosomal protein NPC1 or NPC2 cause intracellular accumulation of unester

232 nerative disorder caused by mutations in the NPC1 or NPC2 gene that result in an accumulation of unes

233 afficking defects caused by mutations in the NPC1 or NPC2 gene.

234 Loss of function of NPC1 or NPC2 leads to cholesterol accumulation in late e

235 Deficiency of either NPC1 or NPC2 leads to the accumulation of cholesterol an

236 emann-Pick C (NPC) disease is due to loss of NPC1 or NPC2 protein function that is required for unest

237 degenerative disorder caused by mutations in NPC1 or NPC2 with decreased functions leading to lysosom

238 sease type C (NPC) is caused by mutations in NPC1 or NPC2, which coordinate egress of low-density-lip

239 caused by defects in the lysosomal proteins NPC1 or NPC2.

240 this interaction, in which mAbs specific for NPC1 or the GP receptor-binding site are coupled to a mA

241 Silicon content in NPC1-overexpressing (OE) plants was decreased in nodes b

242 tive to a historical comparison cohort of 21 NPC1 participants of similar age range.

243 Affected NPC1 patients and NPC1 heterozygote carriers had reduced

244 erapy may represent a therapeutic option for NPC1 patients and suggest that extraneuronal NPC1 expres

245 tric identified a potential adverse event in NPC1 patients receiving i.v. cyclodextrin therapy.

246 nces in the NMR plasma metabolic profiles of NPC1 patients when compared to healthy controls.

247 ic trial of short-term NAC administration to NPC1 patients, no significant effects on oxidative stres

248 nt mouse brains and the human fibroblasts of NPC1 patients.

249 eted proteins with increased serum levels in NPC1 patients: galectin-3 (LGALS3), a pro-inflammatory m

250 e stress-related mechanism in progression of NPC1 phenotypes and suggesting NAC as a potential molecu

251 ntry occurs upon arrival in Niemann-Pick C1 (NPC1)-positive endolysosomes (LE/Lys), we propose that t

252 is in the cysteine-rich luminal loop of the NPC1 protein and is highly similar to commonly occurring

253 These experiments support a model in which NPC1 protein functions to transfer cholesterol past a ly

254 Quantitation of cellular LAMP2 and NPC1 protein levels suggest that LAMP proteins represent

255 pies directed at stabilization of the mutant NPC1 protein reduce cholesterol storage in fibroblasts b

256 reclinical evaluation of therapies targeting NPC1 protein variants with compromised stability.

257 ain and liver display dramatic reductions in Npc1 protein, as well as abnormal cholesterol metabolism

258 ns in NPC1, which encodes the late endosomal NPC1 protein.

259 d the hypothesis that Niemann-Pick type C 1 (NPC1) protein aids the transfer of low density lipoprote

260 enotype, and (3) inhibit GP-Niemann-Pick C1 (NPC1) protein interaction.

261 Niemann-Pick C1 (NPC1) protein is an essential filovirus receptor that bi

262 llular receptors, including Niemann-Pick C1 (NPC1) protein, and GP2 is responsible for low pH-induced

263 Conversely, the Niemann-Pick C1 (NPC1) protein, which regulates cholesterol export from t

264 GP, and its entry receptor Niemann-Pick C1 (NPC1) provides an attractive target for such mAbs but is

265 Hepatic NPC1 re-expression did not ameliorate the onset and prog

266 likely represents the binding site of their NPC1 receptor.

267 ed to wild-type, whereas RNAi suppression of NPC1 resulted in the opposite changes to those of NPC1-O

268 h AAV9-EF1a-NPC1, as compared to AAV9-CamKII-NPC1, resulted in significantly increased survival (mean

269 However, unlike NPC1, RIDalpha did not reconstitute transport to endopla

270 e fibre cells than wild-type plants; whereas NPC1-RNAi plants displayed the opposite changes.

271 ed domain (MLD) and transfers cholesterol to NPC1's N-terminal domain (NTD).

272 NPC2 binds to NPC1's second (middle), lumenally oriented domain (MLD)

273 stricted to cells that have primate-specific NPC1 sequences at the EBOV interface, suggesting that th

274 of cholesterol from lysosomes by U18666A or NPC1 siRNA prevents ER cholesterol from increasing and,

275 these difficulties, the search for a novel, NPC1-specific biomarker (or set of biomarkers) is a topi

276 f the NPC1-NPC2 complex onto the full-length NPC1 structure reveals a direct cholesterol transfer tun

277 odels, findings that were confirmed in human NPC1 subjects receiving HP-beta-CD.

278 also interfered with the binding of TIM-1 to NPC1, suggesting that the interaction between TIM-1 and

279 inding Niemann-Pick disease type C1 protein (NPC1) suggests how the modified binding surface of Juno

280 logical findings and significantly increases Npc1(-/-) survival.

281 P-X also cross-linked to purified NPC1 that was incorporated into lipid bilayer nanodiscs.

282 GP without impeding binding of the C-loop of NPC1, the endolysosomal receptor for EBOV.

283 Compared with the Npc1(-/-) mouse, this Npc1(tm(I1061T)Dso) model displays a less severe, delaye

284 ompounds also promoted trafficking of mutant NPC1 to late endosomes and lysosomes and rescued the abe

285 ntributes to controlling the availability of NPC1 to the cell.

286 INTERPRETATION: Patients with NPC1 treated with intrathecal HPbetaCD had slowed diseas

287 s between blood plasma samples acquired from NPC1 (untreated and miglustat treated), heterozygote, an

288 sceptibility in bats, and suggests that some NPC1 variations reflect host adaptations to reduce filov

289 Overexpression of NPC1 was recently demonstrated to rescue GP-F88A-mediate

290 ast, expression of Mer, integrin alphaV, and NPC1 was required for efficient GP-mediated transduction

291 t the potential efficacy of gene therapy for NPC1, we constructed adeno-associated virus serotype 9 (

292 2013, and Jan 19, 2015, 32 participants with NPC1 were assessed for eligibility at the National Insti

293 P-X cross-linked to NPC1 when added to intact cells.

294 Niemann-Pick disease, type C1 (NPC1), which arises from a mutation in the NPC1 gene, is

295 nted by deletion of the N-terminal domain of NPC1, which contains the initial binding site for choles

296 NPC) is caused in most cases by mutations in NPC1, which encodes the late endosomal NPC1 protein.

297 amino acid change in the filovirus receptor, NPC1, which greatly reduces the affinity of EBOV-NPC1 in

298 In contrast to NPC1, which is dispensable, the RIDalpha/ORP1L-dependent

299 In this study, we demonstrate that TIM-1 and NPC1, which serve as attachment and fusion receptors for

300 ly intrathecal HPbetaCD to participants with NPC1 with neurological manifestation at the National Ins