ライフサイエンスコーパス: PrP

1 PrP ligands could theoretically antagonize prion formati

2 PrP(C) may also act as a receptor for neurotoxic, oligom

3 PrP(C) may be shed from the cell surface to generate sol

4 PrP(L-BSE) associated seeding activity was detected at e

5 PrP(Sc) resistance to proteinase K (PrP(res)), residual

6 We demonstrate that <25% PrP suppression is sufficient to extend survival and del

7 pply a method for monitoring the effect of a PrP-reducing drug in the CNS, and will facilitate develo

8 5 days old) spontaneously generated abnormal PrP assemblies, which after inoculation into further gro

9 tulate our previous findings with additional PrP-targeting ASOs, and demonstrate therapeutic benefit

10 tein (PrP), act as lethal infectious agents, PrP amyloid fibrils produced in vitro generally do not.

11 Membrane-anchored PrP(C) and neural cell adhesion molecule were not requir

12 phosphatidylinositol-anchored (GPI-anchored) PrP was relatively unchanged, forming diffuse, HS-defici

13 regarding the interaction between Zn(2+) and PrP(C), there is little direct spectroscopic confirmatio

14 express comparable levels of PrP(A116V) and PrP(C) respectively, displayed similar increases in Abet

15 velop amyloid-beta (Abeta) plaques of AD and PrP (specifically mutated PrP(A116V)) plaques of Gerstma

16 rimary human TM cells and human, bovine, and PrP-knock-out (PrP(-/-)) mouse models, we demonstrate th

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

18 sults support ASO-mediated PrP lowering, and PrP-lowering therapeutics in general, as a promising pat

19 l interplay between CWD prion plasticity and PrP(C) polymorphisms during prion strain evolution.

20 f tau-based assays for Alzheimer's seeds and PrP-based assays for prions were best in weakly hydrated

21 b disease (CJD), we applied 3 different anti-PrP antibodies.

22 Here we show that the anti-PrP mAb PRC7 recognizes an epitope that is shielded from

23 Clinical development of any PrP-reducing therapeutic will require an appropriate pha

24 arly to the amyloid precursor protein (APP), PrP(C) is proteolytically cleaved from the cell surface

25 te into the infectious scrapie form known as PrP(Sc) The high-resolution structure of the infectious

26 C) and inducing its conversion to PrP(Sc) As PrP(Sc) accumulates, cellular stress mechanisms are acti

27 gnition of the peptide by PrP(C), as well as PrP(C)-dependent cellular uptake.

28 tease-resistant self-replicating assemblies (PrP(Sc)).

29 ings indicate that amino acid differences at PrP residue 226 dictate the selection and propagation of

30 a from sCJDMM1-2 (methionine homozygosity at PrP gene codon 129) establishes the type-mixed sCJD vari

31 duction showing a clear dissociation between PrP(res) and infectivity.

32 Both PrP(C) and NgR1 preferentially bound synaptotoxic oligom

33 Both PrP(C) protein and mRNA levels in astrocytes were compar

34 ecifically, the experiments reveal that both PrP(106-126) and hIAPP induced dramatic transformations

35 ed the capacity of AS to propagate in bovine PrP transgenic mice.

36 rom 5 different European countries to bovine PrP mice resulted in the propagation of the classical BS

37 erapeutically meaningful reductions in brain PrP to be readily detected in CSF.

38 noculated animals show detectable skin/brain PrP(Sc) only after long cohabitation periods with scrapi

39 ow that strain characteristics of vCJD brain PrP(D), including infectivity, are preserved in PrP(D) p

40 Prion diseases are caused by PrP(Sc), a self-replicating pathologically misfolded pro

41 in gallate ameliorated vesicle disruption by PrP(106-126).

42 orphology changes of the vesicles induced by PrP(106-126) and hIAPP.

43 d conformational conversion is influenced by PrP(C) polymorphisms.

44 nsible for the recognition of the peptide by PrP(C), as well as PrP(C)-dependent cellular uptake.

45 In contrast to PrP(C), PrP(A116V) weakly co-localized to Abeta plaques, did not

46 cells expressing solely the Delta190-196 C1 PrP construct, in the absence of the full-length protein

47 acking endogenous mouse PrP expression (CAD5-PrP(-/-) cells) can be chronically infected with hamster

48 We conclude that transfected CAD5-PrP(-/-) cells may be a useful tool for assessing the bi

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

50 Cervid PrP(C) contains at least 20 different polymorphic sites.

51 d by chymotrypsin to digest denatured cervid PrP, 19 peptides suitable for multiple reaction monitori

52 transgenic mice expressing different cervid PrP(C) polymorphisms.

53 sitions 30-51, 61-112, and 114-231 of cervid PrP were identified.

54 an polymorphism-containing regions of cervid PrP.

55 ed plaques highly enriched in ADAM10-cleaved PrP and heparan sulfate (HS).

56 ot hamster prions upon expression of cognate PrP, suggesting that CAD5 cells either possess cellular

57 etected when the amount of the corresponding PrP(D) type exceeded 20-25%.

58 th the relative amounts of the corresponding PrP(D) type.

59 in (PrP(C)) into its infectious counterpart (PrP(Sc)) during prion infection remain undetermined, in

60 that blood contamination does not affect CSF PrP levels, and that CSF PrP and hemoglobin are uncorrel

61 cohort with controlled sample handling, CSF PrP exhibits good within-subject test-retest reliability

62 does not affect CSF PrP levels, and that CSF PrP and hemoglobin are uncorrelated, together suggesting

63 e uncorrelated, together suggesting that CSF PrP is CNS derived, supporting its relevance for monitor

64 We show that CSF PrP is highly sensitive to plastic adsorption during han

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

66 infected with prions significantly decreased PrP(Sc) accumulation.

67 oding sequence was replaced with elk or deer PrP, we show that the resulting GtE226 and GtQ226 mice h

68 CR deletion generates toxicity, we designed PrP(C) constructs wherein either the cis-interaction or

69 S samples, whereas western blotting detected PrP(Sc) in the sciatic nerve in one VV2 and one MV2K.

70 s animals facilitate conversion of different PrP(C) polymorphisms into PrP(Sc).

71 tection, prion infection leads to diminished PrP(Sc) glycosylation at Asn-196, resulting in an unshie

72 hat transmission through hosts with distinct PrP(C) sequences diversifies the PrP(CWD) conformations

73 tional standard manipulations to distinguish PrP(Sc) from PrP(C), including evaluation of protease re

74 While deer and elk PrP primary structures are equivalent except at residue

75 a neuroblastoma cells ablated for endogenous PrP expression were susceptible to mouse prions, but not

76 ermination, are maintained in urine excreted PrP(D) and following amplification by PMCA.

77 rict prion replication, distinct co-existing PrP(CWD) conformers underwent competitive selection, sta

78 ion protein (PrP(C)) into cytotoxic fibrils (PrP(Sc)).

79 man AD brains revealed a strong affinity for PrP(C), weak affinity for NgR1, and no detectable affini

80 ngs further establish a structural basis for PrP(C)'s C-terminal regulation of its otherwise toxic N

81 inal fluid (CSF) to serve as a biomarker for PrP-reducing therapeutics.

82 Detection efficiency for PrP-96S homozygous animals was substantially lower, sugg

83 cence analysis indicated similar results for PrP(Sc) Interestingly, when we used prion conversion act

84 previously been proposed as a treatment for PrP prion disorders.

85 rd manipulations to distinguish PrP(Sc) from PrP(C), including evaluation of protease resistance.

86 Furthermore, PrP(D) characteristics analyzed by immunoblot and confor

87 ral instability of incompletely glycosylated PrP contributes to the conformational conversion of PrP(

88 had prolonged incubation periods and greater PrP(Sc) fibril stability compared to mice challenged wit

89 n required absence of mouse PrP, and hamster PrP inhibited the propagation of mouse prions.

90 infectious to naive cells expressing hamster PrP.

91 rions following stable expression of hamster PrP.

92 Hence, PrP* arrives at the plasma membrane in complex with ER-d

93 benefit similar to constitutive heterozygous PrP knockout.

94 tissue of interest and in keeping with high PrP abundance in brain relative to blood.

95 ings from transgenic mice that express human PrP 117V on a mouse PrP null background (117VV Tg30 mice

96 ansgenic models expressing only mutant human PrP has not been demonstrated.

97 ransgenic model expressing only mutant human PrP to show spontaneous generation of transmissible PrP

98 ated transgenic mice expressing normal human PrP with amplified urine and brain homogenate achieving

99 ntial of ELISA-based quantification of human PrP in human cerebrospinal fluid (CSF) to serve as a bio

100 studies provide insight into how PTMs impact PrP interactions with polyanionic cofactors, and highlig

101 s been observed to drive tertiary contact in PrP(C), inducing a neuroprotective cis interaction that

102 ocular pressure is significantly elevated in PrP(-/-) mice relative to wild-type controls, suggesting

103 esults shed new light on the roles of NAs in PrP misfolding and TSEs.

104 mpared with an extracellular predominance in PrP(C)-expressing mice (TgAD, TgAD/HuPrP).

105 (D), including infectivity, are preserved in PrP(D) present in urine and are faithfully amplified by

106 Further uptake stereodifferentiation in PrP(C)-free cells points toward additional receptor-medi

107 ink encephalopathy uncovered that incomplete PrP(Sc) glycosylation is a consistent feature of prion p

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

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

110 In contrast, infectious PrP rods are 20 nm wide and contain two fibres, each wit

111 o examine the structure of highly infectious PrP rods isolated from mouse brain in comparison to non-

112 The structure of the infectious PrP rods, which cause lethal neurodegeneration, readily

113 high-resolution structure of the infectious PrP(Sc) state remains unknown, and its analysis largely

114 ed by Zn(2+) is thought to regulate inherent PrP(C) toxicity.

115 indings not only provide deeper insight into PrP(C) metal ion coordination but they also suggest new

116 rsion of different PrP(C) polymorphisms into PrP(Sc).

117 Intracellular PrP(Sc) aggregates primarily accumulate within late endo

118 e proteomics revealed a remarkably invariant PrP* interactome during its trafficking from the endopla

119 otein (PrP(C)) into the pathological isoform PrP(Sc) Elucidating the molecular and cellular mechanism

120 PrP(Sc) resistance to proteinase K (PrP(res)), residual infectivity by mouse bioassay and in

121 gate some biophysical properties of the L132 PrP(Sc) conformation.

122 intracellular Abeta plaques in mice lacking PrP(C) (TgAD/PrP(-/-), TgAD/GSS) compared with an extrac

123 reduction was lower than in neurons lacking PrP(C) under the same conditions.

124 n of the deglycosylated forms of full-length PrP(C) and its C-terminal cleavage fragments C1 and C2,

125 teolysis are of interest because full-length PrP(C) and its cleavage fragments differ in their propen

126 L132 elk is a novel CWD strain and that M132 PrP(C) is able to propagate some biophysical properties

127 hat antisense oligonucleotide (ASO)-mediated PrP suppression extends survival and delays disease onse

128 These results support ASO-mediated PrP lowering, and PrP-lowering therapeutics in general,

129 disruption of this interaction by misfolded PrP oligomers may be a cause of toxicity in prion diseas

130 We hypothesized that ADAM10-modulated PrP(C) shedding would alter the cellular binding and cyt

131 lecular weight range approximating monomeric PrP (mM1000) generated through size exclusion chromatogr

132 mice that express human PrP 117V on a mouse PrP null background (117VV Tg30 mice), which model the P

133 ate that CAD5 cells lacking endogenous mouse PrP expression (CAD5-PrP(-/-) cells) can be chronically

134 Examination of the mutation E199K in mouse PrP(C) (E200K in humans), responsible for inherited Creu

135 prion replication required absence of mouse PrP, and hamster PrP inhibited the propagation of mouse

136 ng a gene-targeting approach where the mouse PrP coding sequence was replaced with elk or deer PrP, w

137 the generation of disease-related multichain PrP assemblies that propagate by seeded protein misfoldi

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

139 st the globular domain of recombinant murine PrP (rPrP(90-231)) using SELEX methodology.

140 plaques of AD and PrP (specifically mutated PrP(A116V)) plaques of Gerstmann-Straussler-Scheinker di

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

142 erstanding the function of the nonpathogenic PrP(C) monomer is an important objective.

143 vealed a direct dependence on PrP(C) but not PrP(A116V) for exosome-related secretion of Abeta.

144 tometry analysis showed that at least 85% of PrP* molecules transiently access the plasma membrane en

145 istance to aqueous outflow in the absence of PrP(C).

146 Thus, intracellular accumulation of PrP(Sc) aggregates has the potential to globally influen

147 The administration of PrP(Sc) causes a robust, reproducible and specific disea

148 his study is the first to report analysis of PrP(C) using such an approach.

149 Despite the reduced association of PrP(A116V) with Abeta, TgAD/GSS and TgAD/HuPrP mice that

150 methods in an effort to discover binders of PrP, including (19)F-observed and saturation transfer di

151 s, it is likely that concomitant cleavage of PrP(C) exaggerates and confounds the pathology by induci

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

153 Prions are composed of PrP(Sc), a misfolded version of the cellular prion prote

154 onfirming the extremely low concentration of PrP(D) in vCJD urine.

155 tributes to the conformational conversion of PrP(C) to PrP(Sc).

156 The conserved central region (CR) of PrP(C) has been hypothesized to serve as a passive linke

157 The morphologically diverse deposition of PrP(Sc) in genetic and sporadic CJD argues against unifo

158 rein, we studied a recombinant derivative of PrP(C) (soluble cellular prion protein, S-PrP) that corr

159 erved histidines in the C-terminal domain of PrP(C) are essential for the protein's cis interaction,

160 markers can be reversed by a single dose of PrP-lowering ASO administered after the detection of pat

161 of T2, inferring a conformational effect of PrP(D) T2 on T1(21).

162 rotein is a misfolded and aggregated form of PrP(C) responsible for prion-induced neurodegenerative d

163 nds closely in sequence to a soluble form of PrP(C) shed from the cell surface by proteases in the A

164 these results demonstrate that shed forms of PrP(C) may exhibit important biological activities in th

165 that the CR facilitates homodimerization of PrP(C) , attenuating the toxicity of the N-terminus.

166 A comparison of the infectivity of PrP(Sc) attached to SMA lipid particles in mice and hams

167 as also applied to examine the inhibition of PrP(106-126)-membrane interactions by epigallocatechin g

168 HuPrP mice that express comparable levels of PrP(A116V) and PrP(C) respectively, displayed similar in

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

170 Heated strains showed a huge loss of PrP(res) and a radically different infectivity loss: RML

171 screening pipeline to identify modulators of PrP(C) expression levels or proteolysis.

172 Modulators of PrP(C) proteolysis are of interest because full-length P

173 e cell-surface anchored C-terminal moiety of PrP generated by natural cellular processing.

174 The oligomerization of PrP in mM1000 could be substantially mitigated by treatm

175 d conditions and highlight the prominence of PrP(C) as an Abeta-binding site.

176 against uniform mechanisms of propagation of PrP(Sc) .

177 to the flexible, N-terminal repeat region of PrP(C) and drives a tertiary contact between this repeat

178 evidence that the 113 C-terminal residues of PrP are sufficient for a self-propagating prion entity.

179 so provide support for a fundamental role of PrP(C) to bind to and deliver intraneuronal Abeta to exo

180 s indicate that by promoting the shedding of PrP(C) in human neurons, ADAM10 activation prevents the

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

182 Silencing of PrP(C) in primary human TM cells induces aggregation of

183 Analysis of (113)Cd NMR spectra of PrP(C), along with relevant control proteins and peptide

184 Chronic ASO-mediated suppression of PrP beginning at any time up to early signs of neuropath

185 the role of the H2 alpha-helix C terminus of PrP, we found that deletion of the highly conserved (190

186 APPswe cells revealed a direct dependence on PrP(C) but not PrP(A116V) for exosome-related secretion

187 hat Abeta (1-30) uptake is also dependent on PrP(C) expression.

188 reening of compound libraries for effects on PrP(C) proteolysis or overall expression level.

189 racterization identified the docking site on PrP(C) that underlies the stereoselective binding of Abe

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

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

192 stion of nucleic acids, whereas higher-order PrP assemblies derived from pooled mM1000, oM1000, and o

193 xpressing either the mutant protein or other PrPs with slightly different deletions in the same area.

194 cells and human, bovine, and PrP-knock-out (PrP(-/-)) mouse models, we demonstrate that PrP(C) is ex

195 conserved (190)HTVTTTT(196) segment of ovine PrP led to spontaneous prion formation in the RK13 rabbi

196 y was also detected in brain tissue of ovine PrP mice inoculated with limiting dilutions (endpoint ti

197 re caused by the conversion of physiological PrP(C) into the pathogenic misfolded protein PrP(Sc), co

198 Prions (PrP(Sc)) replicate by inducing a normal cellular prion p

199 During disease progression, PrP(Sc) replicates by interacting with PrP(C) and induci

200 in, which up-regulates ADAM10, also promoted PrP(C) shedding and decreased AbetaO binding in the neur

201 NAs modulates phase separation and promotes PrP fibrillation in a NA structure and concentration-dep

202 th the muscarinic agonist carbachol promotes PrP(C) shedding and reduces the binding of AbetaO to the

203 PrP(C) into the pathogenic misfolded protein PrP(Sc), conferring new properties to PrP(Sc) that vary

204 mely, the 106-126 fragment of prion protein (PrP(106-126)) and the human islet amyloid polypeptide (h

205 sition 163 of canine cellular prion protein (PrP(C) ) is a major determinant of the exceptional resis

206 The cellular prion protein (PrP(C)) comprises two domains: a globular C-terminal dom

207 the past decade, the cellular prion protein (PrP(C)) has emerged as an important mediator of Abeta-in

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

209 he misfolding of the cellular prion protein (PrP(C)) into cytotoxic fibrils (PrP(Sc)).

210 tional conversion of cellular prion protein (PrP(C)) into its infectious counterpart (PrP(Sc)) during

211 ctural conversion of cellular prion protein (PrP(C)) into scrapie PrP (PrP(Sc)) and subsequent aggreg

212 by misfolding of the cellular prion protein (PrP(C)) into the pathological isoform PrP(Sc) Elucidatin

213 The cellular prion protein (PrP(C)) is a glycoprotein that is processed through seve

214 The cellular prion protein (PrP(C)) is a key neuronal receptor for beta-amyloid olig

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

216 Cellular prion protein (PrP(C)) is a widely expressed glycosylphosphatidylinosit

217 The cellular prion protein (PrP(C)) is a zinc-binding protein that contributes to th

218 species that express cellular prion protein (PrP(C)) molecules varying in amino acid composition.

219 by inducing a normal cellular prion protein (PrP(C)) to adopt the prion conformation.

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

221 , we investigated whether the prion protein (PrP(C)), a neuronal protein known to modulate epithelial

222 beta receptors, only cellular prion protein (PrP(C)), Nogo receptor 1 (NgR1), and leukocyte immunoglo

223 olded version of the cellular prion protein (PrP(C)).

224 of abnormal, disease-related prion protein (PrP(D)) has recently been demonstrated by protein misfol

225 To detect disease-associated prion protein (PrP(Sc) ) in the vagus nerve in different forms and mole

226 psies and looked for abnormal prion protein (PrP(Sc)) by western blotting and real-time quaking-induc

227 perties of disease-associated prion protein (PrP(Sc)).

228 uestion of cross-talk between prion protein (PrP) and Alzheimer's disease (AD), we generated TgAD/GSS

229 e gene gives rise to a single prion protein (PrP) capable of converting into the sole causal disease

230 Lowering of prion protein (PrP) expression in the brain is a genetically validated

231 coding mutations in the human prion protein (PrP) gene (PRNP) and account for about 15% of human prio

232 tau, alpha-synuclein, and the prion protein (PrP) induced by aggregates in biospecimens.

233 ering knockin mice expressing prion protein (PrP) lacking 2 N-linked glycans (Prnp180Q/196Q), we prov

234 Reduction of native prion protein (PrP) levels in the brain is an attractive strategy for t

235 a pharmacologically tractable Prion Protein (PrP) signaling cascade.

236 ormational corruption of host prion protein (PrP) to its infective counterpart, contagious transmissi

237 ic mouse model expressing dog prion protein (PrP) was generated and challenged intracerebrally with a

238 ies of misfolded host-encoded prion protein (PrP), act as lethal infectious agents, PrP amyloid fibri

239 olding and aggregation of the prion protein (PrP), and there are currently no therapeutic options.

240 of the host-encoded cellular prion protein (PrP), leading to the formation of beta-sheet-rich, insol

241 forms of the normal cellular prion protein (PrP).

242 We have used misfolded prion protein (PrP*) as a model to investigate how mammalian cells reco

243 ozygosity at codon 129 of the prion protein, PrP, gene harboring disease-related PrP, PrP(D), types 1

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

245 lar prion protein (PrP(C)) into scrapie PrP (PrP(Sc)) and subsequent aggregation are key events assoc

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

247 D), high (TgAD/HuPrP), or no (TgAD/PrP(-/-)) PrP(C).

248 in, PrP, gene harboring disease-related PrP, PrP(D), types 1 and 2).

249 practical and robust method for quantifying PrP, and reliably demonstrating its reduction in the cen

250 Detection of PRC7-reactive PrP(Sc) in experimental and natural infections with vari

251 Non-infectious recombinant PrP fibrils are 10 nm wide single fibres, with a double

252 in comparison to non-infectious recombinant PrP fibrils generated in vitro.

253 ely, siRNA-mediated ADAM10 knockdown reduced PrP(C) shedding and increased AbetaO binding, which was

254 protein, PrP, gene harboring disease-related PrP, PrP(D), types 1 and 2).

255 propagated high levels of protease-resistant PrP.

256 S-PrP activated cell-signaling in PC12 and N2a cells.

257 S-PrP promoted PC12 cell neurite outgrowth.

258 In Schwann cells, S-PrP interacted with the LRP1/NMDA-R system to activate e

259 ll adhesion molecule were not required for S-PrP-initiated cell-signaling.

260 The effects of S-PrP on PC12 cell neurite outgrowth and Schwann cell migr

261 of PrP(C) (soluble cellular prion protein, S-PrP) that corresponds closely in sequence to a soluble f

262 cellular prion protein (PrP(C)) into scrapie PrP (PrP(Sc)) and subsequent aggregation are key events

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

264 Since PrP(C) is cleaved by members of the disintegrin and matr

265 sPMCA detects skin PrP(Sc) as early as 2 weeks post inoculation (wpi) in ha

266 Whereas some PrP amino acid variants cause the disease, others confer

267 r Abeta plaques in mice lacking PrP(C) (TgAD/PrP(-/-), TgAD/GSS) compared with an extracellular predo

268 ormal (TgAD), high (TgAD/HuPrP), or no (TgAD/PrP(-/-)) PrP(C).

269 (PrP(-/-)) mouse models, we demonstrate that PrP(C) is expressed in the TM of all three species, incl

270 We show here that PrP undergoes LLPS, and that the PrP interaction with NA

271 our findings are two-fold; they suggest that PrP expression augments Abeta plaque production, at leas

272 formation of PrPSc plaques and suggest that PrP posttranslational modifications direct pathogenicity

273 lly low hit rate observed here suggests that PrP is a difficult target for small-molecule binders.

274 y metal ion-promoted interaction between the PrP(C) N- and C-terminal domains.

275 sed AbetaO binding, which was blocked by the PrP(C)-specific antibody 6D11.

276 th distinct PrP(C) sequences diversifies the PrP(CWD) conformations and causes a shift toward oligome

277 Importantly, the PrP(C) C-terminal fragment C1 does not contain the repor

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

279 sue of whether strain characteristics of the PrP(D) present in vCJD brains, such as infectivity and p

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

281 infected WTD coding one or two copies of the PrP-96S polymorphic variant.

282 w here that PrP undergoes LLPS, and that the PrP interaction with NAs modulates phase separation and

283 ans of PMCA; moreover, they suggest that the PrP(D) urine test might allow for the diagnosis and iden

284 These PrP(C) polymorphisms can affect prion transmission, dise

285 Thus, PrP(Sc) in CJD affects the vagus nerve analogously to al

286 e oxygen species caused by AbetaO binding to PrP(C) Besides blocking AbetaO binding and toxicity, aci

287 o the conformational conversion of PrP(C) to PrP(Sc).

288 In contrast to PrP(C), PrP(A116V) weakly co-localized to Abeta plaques,

289 g with PrP(C) and inducing its conversion to PrP(Sc) As PrP(Sc) accumulates, cellular stress mechanis

290 rotein PrP(Sc), conferring new properties to PrP(Sc) that vary upon prion strains.

291 Peripheral neuropathy, likely related to PrP(Sc) deposition, belongs to the phenotypic spectrum o

292 olymorphism comprised 75 +/- 5% of the total PrP from the G(96)/S(96) heterozygotes.

293 show spontaneous generation of transmissible PrP assemblies that directly mirror those generated in a

294 formation of disease-relevant, transmissible PrP assemblies in transgenic models expressing only muta

295 lly, knockin mice expressing triglycosylated PrP (Prnp187N) challenged with a plaque-forming prion st

296 N-linked glycosylation shields or unshields PrP epitopes from antibody recognition, it dispenses wit

297 D and 7 of 30 genetic CJD cases showed vagal PrP(Sc) immunodeposits with distinct morphology.

298 We observed that whereas PrP(C) is predisposed to full glycosylation and is there

299 Here, we asked whether PrP undergoes liquid-liquid phase separation (LLPS) and

300 sion, PrP(Sc) replicates by interacting with PrP(C) and inducing its conversion to PrP(Sc) As PrP(Sc)