ライフサイエンスコーパス: PrP

1 PrP(C) cell-surface expression was reduced by down-regul

2 PrP(C) contributes to increased proliferation, cell-matr

3 PrP(C) is expressed on the basolateral membrane of retin

4 PrP(C) misfolds to a pathogenic isoform PrP(Sc), the cau

5 PrP(C) protein is also strongly released from schwannoma

6 PrP(C) was degraded via the proteasome pathway mediated

7 PrP(C), laminin, and metabotropic glutamate receptor 5 (

8 PrP(C), the cellular isoform of the prion protein, serve

9 PrP(Sc) sialylation was found to be critical for effecti

10 conversion, we systematically tested over 40 PrP(C) variants of susceptible and resistant PrP(C) sequ

11 nsistent with a neuronal function for Abetao/PrP(C) signaling, plaque density, microgliosis, and astr

12 rity between the infectious prion aggregate, PrP(Sc), and the cellular prion protein of the host, PrP

13 Misfolded prion protein aggregates (PrP(Sc)) show remarkable structural diversity and are as

14 Altered PrP solubility consistent with significantly reduced PrP

15 Although PrP(CWD) was not detected by either method in the initia

16 nal upregulation of NMDARs, we also analyzed PrP knock-out (KO) mice.

17 n where cells expressing either GPI-anchored PrP(C) or transmembrane-anchored PrP(C), which partition

18 Only GPI-anchored PrP(C) supported persistent PrP(res) propagation.

19 nce of endogenous expression of GPI-anchored PrP(C) To further explore these questions, constructs co

20 ein, PrP(res) We show that only GPI-anchored PrP(C) was able to convert to PrP(res) and able to seria

21 ion of transmembrane PrP(C) and GPI-anchored PrP(res) in distinct membrane environments.

22 PI-anchored PrP(C) or transmembrane-anchored PrP(C), which partitions it to a different location, wer

23 HXMS studies revealed that GPI-anchorless PrP(Sc) is characterized by substantially higher protect

24 vivo transmission barrier between PrP(a) and PrP(b).

25 us pathological amyloids including Abeta and PrP(Sc) suggest PMEL is an excellent model system to stu

26 as sCJDMM2, which share 129 MM genotype and PrP(Sc) type 2 but are associated with quite distinct ph

27 down facilitated the interaction of GP78 and PrP(C), thereby increasing PrP(C) ubiquitination.

28 r pathways underlying PrP(Sc) metabolism and PrP(C) function.

29 Anti-PrP antibodies targeting epitopes in the C-terminal doma

30 ministration of FRET donor and acceptor anti-PrP(C) antibodies to living cells yielded a measure of P

31 es and performed serial necropsies to assess PrP(CWD) tissue distribution by real-time quaking-induce

32 Because PrP depletion may result in functional upregulation of N

33 ate the in vivo transmission barrier between PrP(a) and PrP(b).

34 of temporal and spatial correlation between PrP(Sc) and cytotoxicity suggests the contribution of ho

35 al significance of such interactions between PrP(C) and disease-associated amyloid-beta species will

36 M6PR (mannose 6-phosphate receptor) blocked PrP(C) internalization, whereas down-regulation of GIT2

37 on of the buried histidine destabilizes both PrP variants, but produces a more drastic effect in the

38 t is composed of significant amounts of both PrP polymorphisms.

39 a denaturation experiments performed on both PrP variants at neutral and low pH, and correlates with

40 Terminal disease is characterized by PrP(CWD) accumulation in the brain and lymphoid tissues

41 imer's disease toxicity could be governed by PrP(C), a partial, but still therapeutically useful, rol

42 , suggesting that impaired uptake of iron by PrP(Sc) combined with inflammation results in retinal ir

43 techolaminergic neurons remains unchanged by PrP(C) reduction after disease onset.

44 sgenic mice that overexpress hamster PrP(C), PrP(C) overexpression accelerated recombinant PrP fibril

45 Scrapie infection causes PrP(Sc) accumulation and microglial activation, and surp

46 An elevated expression in CD230/PrP(C) was observed in serum-deprived cells in associati

47 pression of the cellular prion protein CD230/PrP(C) and the immunosuppressive cell surface enzyme ect

48 g feature of prion formation is that certain PrP(C) sequences, such as that of bank vole, can be conv

49 uced transgenic (Tg) mice expressing cognate PrP(C) Although disease transmission to only a subset of

50 re, we show that a C-terminal conformational PrP(Sc)-specific antibody reacts differently to three mu

51 sults show that heterozygous animals contain PrP(Sc) that is composed of significant amounts of both

52 In contrast, PrP(C) containing a GPI anchor from which the sialic aci

53 To begin, we produced control PrP(Sc) from PrP(C) using protein misfolding cyclic ampl

54 vealing an essential mechanism that controls PrP(C) levels in CRC.

55 sociated, disease-causing prion protein (Ctm)PrP, increased ALIX and ALG-2 levels are detected along

56 TgD expressing deer PrP(C) was similarly refractory to deer prions from dise

57 find that peroxymonosulfate rapidly degrades PrP(TSE) from two species.

58 culated intraperitoneally with brain-derived PrP(Sc) or PrP(Sc) produced in PMCAb or dsPMCAb and then

59 cking of brain-, PMCAb-, and dsPMCAb-derived PrP(Sc) to secondary lymphoid organs was monitored in wi

60 een and lymph nodes, whereas dsPMCAb-derived PrP(Sc) was found predominantly in liver.

61 e, whereas administration of dsPMCAb-derived PrP(Sc) with reduced sialylation did not cause prion dis

62 mals inoculated with brain- or PMCAb-derived PrP(Sc) developed prion disease, whereas administration

63 after inoculation, brain- and PMCAb-derived PrP(Sc) were found in spleen and lymph nodes, whereas ds

64 Desialylated PrP(C) was less sensitive to cholesterol depletion than

65 The presence of desialylated PrP(C) in neurons caused the dissociation of cytoplasmic

66 same method but with partially desialylated PrP(C) as a substrate (dsPMCAb).

67 e sialic acid had been removed (desialylated PrP(C)) was not converted to PrP(Sc).

68 aque brain and optic nerve tissues to detect PrP.

69 he flexible N-terminal tail of PrP, exhibits PrP-WT-like protective properties.

70 ulting prions transmitted to mice expressing PrP(C) from the species of prion origin, demonstrating t

71 GP78 was identified as the ubiquitinase for PrP(C), thereby revealing an essential mechanism that co

72 ciation of cytoplasmic phospholipase A2 from PrP-containing membrane rafts and reduced the activation

73 r were expressed in a cell line derived from PrP knockout hippocampal neurons, NpL2.

74 The formation of infectious prions from PrP molecules in vitro has required cofactors and/or unp

75 To begin, we produced control PrP(Sc) from PrP(C) using protein misfolding cyclic amplification wit

76 ation with beads (PMCAb), and also generated PrP(Sc) with reduced sialylation levels using the same m

77 nd the one partially sharing some of the GSS PrP(Sc) molecular features was inoculated into different

78 in transgenic mice that overexpress hamster PrP(C), PrP(C) overexpression accelerated recombinant Pr

79 s, the P102L mutation in recombinant hamster PrP promoted prion formation when seeded by minute amoun

80 ic amplification of mouse prions using horse PrP(C) also failed to infect TgEq but retained tropism f

81 and the cellular prion protein of the host, PrP(C) A puzzling feature of prion formation is that cer

82 human NTD by the bovine NTD resembled human PrP(c) The requirement for an NTD, but not for the speci

83 TD interacts with other regions of the human PrP(c) to increase promiscuity.

84 Plasma and whole blood (125)I-PrP(Sc) reached maximal levels by 30 min and 3 hr, respe

85 m of Alzheimer's disease (AD) by implicating PrP(C) as a potential therapeutic target for AD.

86 inhibition of glucocerebrosidase activity in PrP-A53T-SNCA mice using the covalent inhibitor condurit

87 P increased in Tg(CJD) mice but decreased in PrP KO mice, indicating divergent changes in hippocampal

88 identify a network of proteins implicated in PrP(C) trafficking and demonstrate the power of this ass

89 our data characterize mediators involved in PrP(c) shedding and the effect of this sPrP(c) on monocy

90 s show the presence of both polymorphisms in PrP(Sc).

91 treatment results in a profound reduction in PrP(C) expression due to a defect in the translocation o

92 L/HIF-1alpha/GP78 axis has a crucial role in PrP(C) accumulation during tumor progression.

93 Similar but less marked changes were seen in PrP KO mice.

94 ls in the cytoplasmic fraction and increased PrP levels in the insoluble fraction are identified in F

95 down-regulation of GIT2 and VPS28 increased PrP(C) internalization.

96 ction of GP78 and PrP(C), thereby increasing PrP(C) ubiquitination.

97 lent-metal-transporter-1 (DMT-1), indicating PrP(C)-mediated iron uptake through DMT-1.

98 r prion protein (PrP(C)) into new infectious PrP(Sc) Interspecies prion transmissibility studies perf

99 ing of the prion protein (PrP(C)) influences PrP(C) misfolding into the disease-associated isoform, P

100 Trials of compounds that inhibit PrP-dependent amyloid-beta toxicity are commencing in hu

101 avoured by a different brain site of initial PrP(Sc) formation in the two diseases.

102 ure was proposed as the basis for initiating PrP conversion, but experimental results have been confl

103 producing a self-replicating, but innocuous PrP(Sc)-like form, termed anti-prion, which can compete

104 by the sialylation status of the inoculated PrP(Sc) Furthermore, this work suggests that the sialyla

105 dues, which helps to understand interspecies PrP propagation on a molecular level.

106 Conversion of PrP(C) into PrP(Sc) is thought to take place at the cell surface or

107 C) with sialylo-GPIs could be recruited into PrP(Sc), whereas PrP(C) with asialo-GPIs inhibited conve

108 Its misfolded isoform PrP(Sc) is the causative agent of prion diseases.

109 PrP(C) misfolds to a pathogenic isoform PrP(Sc), the causative agent of neurodegenerative prion

110 protein (PrP(C)) into the pathologic isoform PrP(Sc) is a key feature in prion pathogenesis.

111 folding into the disease-associated isoform, PrP(res), as well as prion propagation and infectivity.

112 lus), irrespective of the presence of 21 kDa PrP(res) in the inoculum, demonstrating that GSS is a ge

113 subtypes exclusively associated with 6-8 kDa PrP(res) have often been considered as non-transmissible

114 adhesion complexes but, unlike cells lacking PrP, ZIP6 deficiency does not abolish polysialylation of

115 ng cyclic amplification (PMCA), which mimics PrP(C)-to-PrP(Sc) conversion with accelerated kinetics,

116 Mitochondrial PrP(C) was fully processed with mature N-linked glycans

117 ed mitochondria suggested that mitochondrial PrP(C) exists as a transmembrane isoform with the C-term

118 At 3 MPE, PrP(CWD) replication had expanded to all systemic lympho

119 These data also suggest that multiple PrP(C) segments containing Asn/Gln residues may act in c

120 e not subclinical carriers of scrapie, as no PrP(Sc) was detected in brains or spleen of these animal

121 s temporally with microglial activation, not PrP(Sc) accumulation, suggesting that impaired uptake of

122 Tg(CJD) but not PrP KO mice were intrinsically more susceptible than WT

123 ial days (1 and 3) postexposure, we observed PrP(CWD) seeding activity and follicular immunoreactivit

124 heets that encompass residues 139 and 186 of PrP(Sc).

125 The alpha-helix 2 of PrP contains a string of four threonines, which is unusu

126 rP(C) to rafts are crucial to the ability of PrP(C) to propagate as a prion.

127 sm that regulates the functional activity of PrP(C).

128 The amount of PrP(Sc) in the brains and lymphoid tissues of positive p

129 ggregation and the molecular architecture of PrP(Sc) is key to unraveling the pathology of prion dise

130 GPI anchor-directed membrane association of PrP(C) is required for persistent PrP(res) propagation,

131 A similar beta-cleavage of PrP(C) is observed in mouse retinal lysates.

132 of ferritin by 10-fold and beta-cleavage of PrP(C), the latter likely to block further uptake of iro

133 test could detect the low concentrations of PrP probably present in brains of donors at early stages

134 Conversion of PrP(C) into PrP(Sc) is thought to take place at the cell

135 recombinant PrP fibril-induced conversion of PrP(C) to the abnormal proteinase K-resistant state, ref

136 Furthermore, infected cells were cured of PrP(Sc) after exposure of AR-12 or AR-14 for only two we

137 ons and monitored the tissue distribution of PrP(CWD) over the first 4 months of infection.

138 show that the flexible, N-terminal domain of PrP(C) functions as a powerful toxicity-transducing effe

139 t required the globular C-terminal domain of PrP(C), which has not been previously implicated in inte

140 docking between N- and C-terminal domains of PrP(C), revealing a novel auto-inhibitory mechanism that

141 Here, we investigated the effect of PrP(C) on polymerization of Abeta under rigorously contr

142 erves to transduce the neurotoxic effects of PrP(Sc), the infectious isoform, but how this occurs is

143 potent as FK506 in attenuating expression of PrP(C).

144 spontaneous cytotoxicity of a mutant form of PrP (Delta105-125).

145 The precise function of PrP(C) remains elusive but may depend upon its cellular

146 s relevant for understanding the function of PrP.

147 Finally, incubation of PrP(Sc) with recombinant GRP78 led to the dose-dependent

148 pathy, confirming the crucial involvement of PrP(C) in peripheral myelin maintenance.

149 composed solely of this abnormal isoform of PrP (PrP(Sc)).

150 t that GPI anchoring and the localization of PrP(C) to rafts are crucial to the ability of PrP(C) to

151 roduce and especially by the localization of PrP(Sc) deposits within the brain and the spongiform les

152 ibodies to living cells yielded a measure of PrP(C) surface density, whereas sequential addition of e

153 of this assay for identifying modulators of PrP(C) trafficking.

154 and pharmaceutical screens for modulators of PrP(C) trafficking.

155 rrents associated with neurotoxic mutants of PrP, and the isolated N-terminal domain induces currents

156 Accordingly, the neuroretina of PrP-knock-out mice is iron-deficient.

157 Therefore, the organization of PrP molecules in terms of the density of aggregates gene

158 In addition, a strong overexpression of PrP(C) is observed in human Merlin-deficient mesotheliom

159 udy underscores the therapeutic potential of PrP(C) deletion given that patients already present symp

160 pical PrPres, which was the first product of PrP(C) misfolding in vivo.

161 infectious and neuropathogenic properties of PrP-derived aggregates.

162 ibody visualized the internalization rate of PrP(C) (Z' factor >0.5).

163 ssion and real-time internalization rates of PrP(C) The assay is suitable for high-throughput genetic

164 tures in the normally unstructured region of PrP that influence the infectious and neuropathogenic pr

165 Reminiscent of PrP, ZIP6 levels are five-fold upregulated during EMT an

166 Here, we define the role of PrP(C) to rescue or halt established AD endophenotypes i

167 of a particular polymorphism in a sample of PrP(Sc) isolated from sheep heterozygous for their PrP(C

168 We propose that shedding of PrP(c) could be a potential target for therapeutics to l

169 of HIV-infected people, increase shedding of PrP(c) from human astrocytes by increasing the active fo

170 In RPE19 cells, silencing of PrP(C) decreases ferritin while over-expression upregula

171 PrP(res) if seeded by an exogenous source of PrP(res) not associated with host cell rafts and without

172 work suggests that the sialylation status of PrP(Sc) plays an important role in prion lymphotropism.

173 s similar to the flexible N-terminal tail of PrP, exhibits PrP-WT-like protective properties.

174 The targeting of PrP(C) to synapses was dependent upon both neuronal chol

175 h sialylated GPIs prevented the targeting of PrP(C) to synapses.

176 ally, our results identify the C terminus of PrP(C) as a new and potentially more druggable molecular

177 formational differences in the C terminus of PrP(Sc) also contribute to the phenotypic distinction be

178 derstanding the intracellular trafficking of PrP(C) may, therefore, help elucidate the conversion pro

179 to be critical for effective trafficking of PrP(Sc) to secondary lymphoid organs.

180 sion due to a defect in the translocation of PrP(C) into the endoplasmic reticulum with subsequent de

181 Among the variety of PrP(C) protein interactors, the neuronal cell adhesion m

182 al animal models, based on the expression of PrPs carrying mutations analogous to human heritable pri

183 sion in Tg(CJD) mice do not depend solely on PrP functional loss.

184 at employed cultured cells claimed that only PrP(C) with sialylo-GPIs could be recruited into PrP(Sc)

185 sitions 136, 154, and 171 of sheep PrP(C) or PrP(Sc).

186 Prions or PrP(Sc) are proteinaceous infectious agents that consist

187 ialoglycoprotein called the prion protein or PrP(C) The current work tests a new hypothesis that sial

188 raperitoneally with brain-derived PrP(Sc) or PrP(Sc) produced in PMCAb or dsPMCAb and then monitored

189 f normal prion protein (PrP) into pathogenic PrP conformers is central to prion disease, but the mech

190 ciation of PrP(C) is required for persistent PrP(res) propagation, implicating raft microdomains as a

191 nly GPI-anchored PrP(C) supported persistent PrP(res) propagation.

192 ses, support that mutations might predispose PrP to spontaneously misfold.

193 Scrapie is a prion (PrP(Sc)) disease of sheep.

194 tor-1alpha (HIF-1alpha) protein and promoted PrP(C) accumulation and tumorigenicity in vivo.

195 , which are composed of a misfolded protein (PrP(Sc)) that self-propagates in the brain of infected i

196 or binding Abeta and cellular prion protein (PrP(C) ), the protein that is thought to have a greater

197 ment, TUDCA-mediated cellular prion protein (PrP(C)) activation was assessed.

198 complex composed of cellular prion protein (PrP(C)) and metabotropic glutamate receptor 5 (mGluR5).

199 PI) membrane anchoring of the prion protein (PrP(C)) directs it to specific regions of cell membranes

200 en proposed that the cellular prion protein (PrP(C)) functions as a cell-surface receptor, which bind

201 given the location of normal prion protein (PrP(C)) in lipid rafts and lipid cofactors generating in

202 reased expression of cellular prion protein (PrP(C)) in schwannoma cells and tissues.

203 ositol (GPI) anchoring of the prion protein (PrP(C)) influences PrP(C) misfolding into the disease-as

204 nsforming the normal cellular prion protein (PrP(C)) into new infectious PrP(Sc) Interspecies prion t

205 ic conversion of the cellular prion protein (PrP(C)) into the pathologic isoform PrP(Sc) is a key fea

206 uals by converting the normal prion protein (PrP(C)) into the pathological isoform.

207 The cellular form of the prion protein (PrP(C)) is a highly conserved glycoprotein mostly expres

208 Cellular prion protein (PrP(C)) is a mammalian glycoprotein which is usually fou

209 cellular isoform of the human prion protein (PrP(c)) is an adhesion molecule constitutively expressed

210 The cellular prion protein (PrP(C)) is associated with metastasis, tumor progression

211 initial report that cellular prion protein (PrP(C)) mediates toxicity of amyloid-beta species linked

212 f the Abetao-binding cellular prion protein (PrP(C)) prevents development of memory deficits in APPsw

213 The normal cellular prion protein (PrP(C)) resides in detergent-resistant outer membrane li

214 -beta-Abetao-binding cellular prion protein (PrP(C)) signaling pathway in a familial form of Alzheime

215 (Sc)), a misfolded isoform of prion protein (PrP(C)) that accumulates in the neuroretina.

216 -encoded cellular form of the prion protein (PrP(C)) to selectively propagate optimized prion conform

217 of a sheep's normal cellular prion protein (PrP(C)).

218 amined for disease-associated prion protein (PrP(Sc)) by Western blotting (WB), antigen capture enzym

219 Disease-associated prion protein (PrP(Sc)) was detected in brain and lymphoid tissues from

220 aused by an abnormally folded prion protein (PrP(Sc)).

221 use solid-state NMR to study prion protein (PrP) amyloids from human, mouse and Syrian hamster and s

222 The prion protein (PrP) evolved from the subbranch of ZIP metal ion transpo

223 at confer transmissibility to prion protein (PrP) fibrils, we have analyzed synthetic PrP amyloids wi

224 range of mutations within the prion protein (PrP) gene.

225 isoform of the host cellular prion protein (PrP) in the brain.

226 The conversion of normal prion protein (PrP) into pathogenic PrP conformers is central to prion

227 generative disorder caused by prion protein (PrP) misfolding, clinically recognized by cognitive and

228 rion seeding and mutations of prion protein (PrP) on the structure and transmission properties of syn

229 Prions derived from the prion protein (PrP) were first characterized as infectious agents that

230 The cellular prion protein, PrP(C), is attached by a glycosylphosphatidylinositol an

231 idylinositol (GPI)-anchorless prion protein, PrP(C), together with hydrogen-deuterium exchange couple

232 tious, misfolded forms of the prion protein, PrP(res) We show that only GPI-anchored PrP(C) was able

233 Ag Kit to detect the abnormal prion protein, PrP.

234 Misofolding of mammalian prion proteins (PrP) is believed to be the cause of a group of rare and

235 osed solely of this abnormal isoform of PrP (PrP(Sc)).

236 onformational properties of the scrapie PrP (PrP(Sc)) grossly identified types 1 and 2.

237 By RT-QuIC, PrP(Sc) was detected in lymphoid and/or brain tissue fro

238 s allowed amino acid substitutions in rabbit PrP and accurate analysis of misfolding propensities.

239 ased the misfolding susceptibility of rabbit PrP.IMPORTANCE Prion disorders are invariably fatal, unt

240 Using recombinant rabbit PrP as a model, this study describes critical molecular

241 tease-resistant misfolded recombinant rabbit PrP was generated.

242 stration, using highly purified radiolabeled PrP(Sc).

243 rP(C) overexpression accelerated recombinant PrP fibril-induced conversion of PrP(C) to the abnormal

244 dology based on the use of human recombinant PrP (recPMCA) generated different self-propagating misfo

245 abbit recombinant PrP from mouse recombinant PrP.

246 Wild-type rabbit recombinant PrP could not be misfolded into a protease-resistant sel

247 tution that distinguishes rabbit recombinant PrP from mouse recombinant PrP.

248 Therefore, rabbit recombinant PrP mutants were designed to contain every single amino

249 were identified that make rabbit recombinant PrP susceptible to misfolding, and using these, protease

250 trypsin was used to digest sheep recombinant PrP to identify a set of characteristic peptides [M132LG

251 r a nonraft transmembrane sequence redirects PrP(C) away from rafts.

252 ed that AR-12 and its analogue AR-14 reduced PrP(Sc) levels after only 72 hours of treatment.

253 bility consistent with significantly reduced PrP levels in the cytoplasmic fraction and increased PrP

254 gnificant changes in the profile of regional PrP(Sc) deposition in the brains of animals that were tr

255 PrP(C) variants of susceptible and resistant PrP(C) sequences in a prion conversion assay.

256 proteinase K (PK)-sensitive and PK-resistant PrP(Sc) and samples containing only the PK-resistant PrP

257 and samples containing only the PK-resistant PrP(Sc).

258 rion seeding activity and protease-resistant PrP without transmissible spongiform encephalopathy (TSE

259 se-dependent reduction of protease-resistant PrP(Sc) in vitro.

260 and conformational properties of the scrapie PrP (PrP(Sc)) grossly identified types 1 and 2.

261 l degeneration is attributed to PrP-scrapie (PrP(Sc)), a misfolded isoform of prion protein (PrP(C))

262 Previously, our laboratory showed that shed PrP(c) (sPrP(c)) is increased in the cerebrospinal fluid

263 isms at positions 136, 154, and 171 of sheep PrP(C) or PrP(Sc).

264 Building on data which suggested PrP and ZIP6 are critical during epithelial-to-mesenchym

265 in (PrP) fibrils, we have analyzed synthetic PrP amyloids with or without the human prion disease-ass

266 ure and transmission properties of synthetic PrP aggregates.

267 se results define the potential of targeting PrP(C) as a disease-modifying therapy for certain AD-rel

268 less sensitive to cholesterol depletion than PrP(C) and was not released from cells by treatment with

269 ld age, mutation, or overexpression and that PrP(C) may affect mitochondrial function.

270 We demonstrated that PrP(C) specifically inhibited elongation of Abeta fibril

271 Our study found that PrP(C) degradation decreased tumor progression in colore

272 Here we show that PrP(C) is present in brain mitochondria from 6-12 week o

273 We suggest that PrP(C) and its interactor, LR/37/67 kDa, could be potent

274 Taken together, our data suggest that PrP(C) can be found in mitochondria in the absence of di

275 Our results suggest that PrP(C) recognizes structural features common to both Abe

276 Our data suggests that PrP and ZIP6 inherited the ability to interact with NCAM

277 Our evidence suggests that PrP's centrally located proline and lysine residues act

278 o diseases, which preferentially involve the PrP(Sc) component that is sensitive to digestion with pr

279 By 4 MPE, the PrP(CWD) burden in all lymphoid tissues had increased an

280 However, the molecular details of the PrP(C)-Abeta interaction remain uncertain.

281 Our detailed comparative study of the PrP(Sc) conformers has revealed major differences betwee

282 We propose that targeting the PrP(C)-mGluR5 complex will reverse aberrant Abetao-trigg

283 ) isolated from sheep heterozygous for their PrP(C) proteins.

284 ciated retinal degeneration is attributed to PrP-scrapie (PrP(Sc)), a misfolded isoform of prion prot

285 embrane PrP(C) variants resist conversion to PrP(res) when transfected into scrapie-infected N2a neur

286 y GPI-anchored PrP(C) was able to convert to PrP(res) and able to serially propagate.

287 hether transmembrane PrP(C) might convert to PrP(res) if seeded by an exogenous source of PrP(res) no

288 d (desialylated PrP(C)) was not converted to PrP(Sc).

289 dues determine high or low susceptibility to PrP(Sc) propagation, protein misfolding cyclic amplifica

290 amplification (PMCA), which mimics PrP(C)-to-PrP(Sc) conversion with accelerated kinetics, was used.

291 us studies showed that nonraft transmembrane PrP(C) variants resist conversion to PrP(res) when trans

292 , likely due to segregation of transmembrane PrP(C) and GPI-anchored PrP(res) in distinct membrane en

293 s, it remained unclear whether transmembrane PrP(C) might convert to PrP(res) if seeded by an exogeno

294 s in the in vitro formation of transmissible PrP amyloids.IMPORTANCE Many diseases involve the damagi

295 C-terminal domains (residues 90-231) of two PrP variants exhibiting different pH-induced susceptibil

296 ols to identify cellular pathways underlying PrP(Sc) metabolism and PrP(C) function.

297 amino-terminal domain of human and bank vole PrP(c)s requires interaction with the rest of the molecu

298 PIs could be recruited into PrP(Sc), whereas PrP(C) with asialo-GPIs inhibited conversion.

299 Furthermore, we examined whether PrP(c) participates in glutamate uptake and found that r

300 ein 78 (GP78), which interacts directly with PrP(C).

301 s that the sialylation status of GPIs within PrP(Sc) is regulated in a cell-, tissue-, or host-specif

302 PrP23-144 (which corresponds to the Y145Stop PrP variant associated with a Gerstmann-Straussler-Schei