ライフサイエンスコーパス: PHF

1 PHF are fibers of amyloid nature that are composed of a

2 PHF are primarily composed of highly phosphorylated tau

3 PHF-Tau from Alzheimer disease brain was affinity-purifi

4 PHF/tau-positive dystrophic neurites were present in and

5 PHFs are composed of microtubule-associated protein tau,

6 PHFs are the first example of pathological aggregation a

7 in VHF and PHF rats (VHF vs. VC, P < 0.001; PHF vs. PC, P < 0.05).

8 hosphorylation at multiple sites (AT8, 12E8, PHF-1, and pS422), tauC3-immunoreactive tau fragmentatio

9 le of tau distributed among approximately 30 PHF phosphorylation sites as compared to 2-3 mol of phos

10 t hyperphosphorylation of Tau at Ser396/404 (PHF-1-reactive Tau, p-Tau), with no changes in pSer202 b

11 we provide clear structural evidence that a PHF, whether found in disease or assembled in vitro, is

12 the insoluble characteristics typical of AD PHF/NFTs.

13 ified but each was indistinguishable from AD-PHFs in mass/nm length and density.

14 ar in mass/nm length, but less dense than AD-PHFs and Pick's disease filaments.

15 f PHF with hydrofluoric acid does not affect PHF solubility.

16 that injection of human wild-type Alzheimer PHF seeded aggregation of wild-type murine tau into an a

17 phorylation-dependent immunoprobes Tau-1 and PHF-1 with the aid of alkaline phosphatase demonstrated

18 hate-dependent anti-tau antibodies Tau-1 and PHF-1, that heat shock induces rapid dephosphorylation o

19 , as recognized by the antibodies PHF-13 and PHF-1, respectively.

20 Tau-1 (Ser-195/Ser-198/Ser-199/Ser-202) and PHF-1 (Ser-396/Ser-404) sites was increased, mostly in t

21 Thereafter, AT-8 and PHF-1 immunoreactivity accumulated in cell bodies and su

22 levant markers of dementia, beta-amyloid and PHF-tau, were profiled in formalin-fixed paraffin embedd

23 Since AT10 and PHF-27 are the only mAbs currently available that bind s

24 Since mAbs AT10 and PHF-27 had little or no affinity for fetal tau and biops

25 With the exception of AT10 and PHF-27, all the mAbs also labeled fetal tau and biopsy-d

26 hosphorylated tau immunostained with AT8 and PHF-1 antibodies.

27 with tau hyperphosphorylation at the AT8 and PHF-1 sites.

28 d later forms of phosphorylated tau (AT8 and PHF-1) in untreated 3xTg-AD mice.

29 ted tau in paired helical filaments (AT8 and PHF-1) show positive immunostaining on days 6-8.

30 endent monoclonal antibodies, tau-1, AT8 and PHF-1, we have found that the dephosphorylation of the a

31 ble-labeling experiments with fodrin CCP and PHF-1 were performed.

32 and throughout subsequent pregnancy (PC and PHF, respectively).

33 le tau phosphoepitopes (AT8, CP13, PT205 and PHF-1).

34 ermine the frequency of occurrence of SF and PHF morphology in filaments assembled from these mutant

35 he liver, the finding of activated Stat3 and PHF/NF-kappa B suggests that these cytokines may play a

36 -wide, 10-75 nm long, frequently twisted and PHF-like filaments, with a mass per unit length (44 kDa/

37 endothelium-dependent relaxation in VHF and PHF rats (VHF vs. VC, P < 0.001; PHF vs. PC, P < 0.05).

38 ma cholesterol, which was reduced in VHF and PHF rats, plasma lipids were normal.

39 Immunohistochemical localization of WT1 and PHF showed the presence of WT1 in approximately 42% of P

40 pecific mAb AT10 and 12 newly developed anti-PHF mAbs that recognize PHF-tau but not autopsy-derived

41 d S396/S404, as recognized by the antibodies PHF-13 and PHF-1, respectively.

42 subsequently recognized by the NFT antibody PHF-1.

43 mulation of disease-related proteins such as PHF-tau in the hippocampus of animals fed the control di

44 ectroscopy to investigate in vitro assembled PHFs from a truncated three-repeat tau isoform (K19) tha

45 Plaque-associated PHF/tau-positive dystrophic neurites were rare or absent

46 increase in phosphorylation was observed at PHF-1 (P-Ser396/P-Thr404), P-Ser202 and P-Thr231 sites o

47 tes recognized by the antibodies AT8, AT100, PHF-1, and TG3.

48 An ABI dependence was found in both PHF (p = 0.04) and TTP (p < 10(-4)).

49 Experiments on K19 C322A PHFs further confirm the influence of disulfide bond for

50 n microscopy (TEM) were used to characterize PHF suspended in Tris-buffered saline (TBS), sodium acet

51 In contrast, PHF(FA) were dephosphorylated at all epitopes, with part

52 In contrast, PHFs from AD were ultrastructurally stable and uniform b

53 Neuronal protective effects and decreased PHF-1 immunoreactivity were observed in two animal model

54 Dephosphorylation of deglycosylated PHF tangles results in increased tau release.

55 fractions of human Alzheimer disease-derived PHFs for 24 h.

56 , retains TAI activity in vitro and disrupts PHFs isolated from AD brain tissues at 0.16 muM.

57 he microtubule-associated protein tau (i.e., PHF-tau).

58 imer disease, play a major role in effecting PHF insolubility in vivo.

59 em mass spectrometry was employed to examine PHF-Tau post-translational modifications, in particular

60 ed to PHF for 1 mo, those who were first fed PHF at 3.5 mo rejected PHF relative to CMF more than did

61 where repeated cases of Potomac horse fever (PHF) have occurred.

62 Horses develop Potomac horse fever (PHF) when they ingest aquatic insects containing encyste

63 risticii, the agent of Potomac horse fever (PHF), from snails (Pleuroceridae: Juga spp.) maintained

64 the causative agent of Potomac horse fever (PHF), which continues to be an important disease of hors

65 ractions leading to paired helical filament (PHF) formation.

66 hemistry of WT1 and paired helical filament (PHF) in serial sections was carried out.

67 The paired helical filament (PHF) is the major component of the neurofibrillary depos

68 rils displaying the paired helical filament (PHF) morphology characteristic of neurofibrillary tangle

69 ated extensively in paired helical filament (PHF) tau from Alzheimer's disease (AD) brain, to a lesse

70 of neuropathology [paired helical filament (PHF)-tau and amyloid-beta] in AD, which typically begins

71 inding affinity for paired helical filament (PHF)-tau pathology in Alzheimer's brains.

72 Paired helical filament (PHF)-tau, alpha-synuclein, and amyloid-beta lesions occu

73 Paired helical filament (PHF)/tau immunoreactive dystrophic neurites are a common

74 Paired helical filaments (PHF) are abnormal, approximately 20-25-nm wide periodica

75 Paired helical filaments (PHF) composed of hyperphosphorylated tau proteins are ch

76 The paired helical filaments (PHF) formed by the intrinsically disordered human protei

77 tes in the form of paired helical filaments (PHF) in the brains of patients with Alzheimer's disease

78 Paired helical filaments (PHF) occur in Alzheimer's diseased brains and are known

79 lubilize insoluble paired helical filaments (PHF) of Alzheimer disease.

80 the biogenesis of paired helical filaments (PHF) seen in Alzheimer's disease.

81 The formation of paired helical filaments (PHF), which are composed of hyperphosphorylated Tau prot

82 Paired helical filaments (PHFs) accumulate in the brains of subjects affected with

83 en I and insoluble paired helical filaments (PHFs) and collagen I of weak hydrogen bonding at proline

84 the generation of paired helical filaments (PHFs) and neurofibrillary tangles, a key neuropathologic

85 Paired-helical filaments (PHFs) are an important diagnostic criterion of the inclu

86 s characterized by paired helical filaments (PHFs) composed of phosphorylated tau.

87 le, which contains paired helical filaments (PHFs) composed of the microtubule-associated protein tau

88 tes into insoluble paired-helical filaments (PHFs) in Alzheimer's disease (AD) and other tauopathies.

89 osphate content of paired helical filaments (PHFs) in Alzheimer's disease (AD) is a result of limited

90 h-molecular-weight paired helical filaments (PHFs) in the dentate gyrus of wild-type and mutant tau T

91 Paired helical filaments (PHFs) in the neurofibrillary tangles (NFTs) in Alzheimer

92 he accumulation of paired helical filaments (PHFs) of hyperphosphorylated microtubule-associated prot

93 e tight bundles of paired helical filaments (PHFs) of tau protein found in Alzheimer's disease (AD) d

94 ein assembles into paired helical filaments (PHFs) that constitute the neurofibrillary tangles observ

95 o the formation of paired helical filaments (PHFs) which deposit into neurofibrillary tangles in Alzh

96 residues found in paired helical filaments (PHFs), and its expression is up-regulated in the brain i

97 mer's disease (AD) paired helical filaments (PHFs), building blocks of neurofibrillary tangles (NFTs)

98 like that found in paired helical filaments (PHFs), does not promote microtubule assembly leading to

99 myloid fibrils and paired helical filaments (PHFs).

100 the Tau MTBR forms paired helical filaments (PHFs).

101 form intraneuronal paired helical filaments (PHFs).

102 rillary tangles of paired helical filaments (PHFs).

103 sphorylated Tau as paired helical filaments (PHFs).

104 to fibers termed "paired helical filaments" (PHFs).

105 nd accumulation of paired helical filaments-(PHF-) like fibrils.

106 Peak hyperemic flow (PHF) and time-to-peak (TTP) were computed and assessed a

107 significantly higher than those reported for PHF found either in AD (0.40 kDa/nm3) or CBD (0.33 kDa/n

108 tion' of PHF proteins is not responsible for PHF insolubility.

109 opment of diagnostic antibodies specific for PHF-tau since elevated tau levels are found in the cereb

110 of tau is either necessary or sufficient for PHF formation.

111 The comparison of FTIR results for PHFs with collagen I gel and polyproline demonstrates th

112 -hydroxymethylethylene hydroxymethyl-formal (PHF), also known as Fleximer.

113 the response to protein hydrolysate formula (PHF) as a model system, we discovered the existence of a

114 ith PHF-tau and fetal tau, but differed from PHF-tau in their lack of the N-terminal insert which cha

115 three principal tau components resolved from PHF-tau on Western blots showed CML immunoreactivity ind

116 lycosylation alone, of AD P-tau and tau from PHF tangles restores their microtubule polymerization ac

117 ever the in vitro glycation of tau generates PHF that are insoluble in SDS and soluble in alkali.

118 However, PHF is occurring in large numbers of horses in spite of

119 hippocampus, indicating that wild-type human PHFs were inefficient in seeding tau aggregates made of

120 tribute to the phosphorylation of Ser 262 in PHF-tau, and thus play a role in the pathogenesis of AD.

121 immunodominant phosphorylated amino acids in PHF-tau.

122 derived hyperpolarizing factor components in PHF rats.

123 bnormal tau aggregation, increased 3-fold in PHF-treated cells.

124 results suggest that tau becomes glycated in PHF-tau and glycation may play a role in stabilizing PHF

125 eactivity indicating that tau is glycated in PHF-tau; and insoluble PHF exhibited prominent CML immun

126 ve stress, 8-iso PGF2alpha, was increased in PHF animals (P < 0.01).

127 particular contact, which may be involved in PHF fibril formation, is proposed here as a possible aro

128 with an important role for beta structure in PHF formation, and may also help explain recent reports

129 Tau is hyperphosphorylated in PHFs, and phosphorylation of tau abolishes its ability t

130 ries of protein solvent to analyze insoluble PHF, only alkali or exhaustive proteolysis are effective

131 at tau is glycated in PHF-tau; and insoluble PHF exhibited prominent CML immunoreactivity on top of t

132 ions of soluble PHF-tau as well as insoluble PHF from AD brains.

133 soluble matrix consistent with the insoluble PHFs/NFTs which may contribute to neuronal degeneration

134 Intact PHFs were effectively dephosphorylated only at the two N

135 studied in vitro dephosphorylation of intact PHFs, PHFs with filamentous structure abolished by formi

136 The results indicate that intact PHFs, but not PHF(FA) or fetal tau display differential

137 The evidence that cells can internalize PHFs, leading to formation of aggresome-like bodies, ope

138 We found that cells internalized PHFs through an endocytic mechanism and developed intrac

139 rain cytosol (AD P-tau) self-aggregates into PHF-like structures on incubation at pH 6.9 under reduci

140 of the molecule can also self-assemble into PHF.

141 s 297-391 of full-length tau) assembles into PHF-like fibrils in vitro without the need for other add

142 AD P-tau inhibits its self-association into PHF.

143 mechanism of initiation of tau assembly into PHFs is not well understood.

144 totic cell death, sequestration of Pin1 into PHFs may contribute to neuronal death.

145 Tau (p-Tau) at the Alzheimer's disease-like PHF-1 phospho-epitope.

146 d Ser214, and the peptide recognition of mAb PHF-27 was markedly increased when both the primary site

147 NFT and was co-localized with the NFT marker PHF-1 and the amyloid P component (AP).

148 at colocalized with the mature tangle marker PHF-1.

149 Moreover, PHFs from CBD have been shown to be primarily composed o

150 at enables reliable identification of muscle PHFs by light microscopy.

151 se in combination with dissolution of native PHFs to quantify the activity of Tau aggregation inhibit

152 e results indicate that intact PHFs, but not PHF(FA) or fetal tau display differential dephosphorylat

153 the presence of WT1 in approximately 42% of PHF-positive neurofibrillary tangle containing-neurons.

154 In the spinal cord, 87% of PHF-1-labeled cells colocalize with the transglutaminase

155 eurites were often present in the absence of PHF/tau-positive plaque-associated dystrophic neurites.

156 tested for Ehrlichia risticii, the agent of PHF, by nested PCR using primers specific to the 16S rRN

157 However, the structural basis of PHF assembly at atomic detail is largely unknown.

158 In a limited study, 43 confirmed cases of PHF occurred between the 1994 and 1996 seasons; of these

159 luorescence to demonstrate colocalization of PHF-1-immunoreactive tau and the transglutaminase-cataly

160 Deglycosylation of PHF tangles by endoglycosidase F/N-glycosidase F convert

161 ate of PHF and complete dephosphorylation of PHF with hydrofluoric acid does not affect PHF solubilit

162 The extent of dephosphorylation of PHF(FA) was equal or more effective than in fetal tau, e

163 d control cases and to examine the effect of PHF accumulation.

164 vation as well as an increased expression of PHF-tau, paralleled by increased levels of reactive oxyg

165 alpha-Syn-dependent, increased formation of PHF-1-reactive Tau, suggesting convergent overlapping pa

166 Module-B likewise result in the formation of PHF-like structures.

167 al antibody to isolate a soluble fraction of PHF-Tau in a conformation unique to human AD brain.

168 he relationship between the heterogeneity of PHF-tau and the appearance of abnormal filaments, the ul

169 s suggest that the 'hyperphosphorylation' of PHF proteins is not responsible for PHF insolubility.

170 The cross-linking of PHF tau occurs both intra-molecularly and inter-molecula

171 beta-strands result in a significant loss of PHF aggregation efficiency, highlighting the importance

172 Three months of PHF exposure led to acceptance similar to that at 1 mo o

173 orresponding matched control preparations of PHF/NFTs, none of these phosphorylated neuronal cytoskel

174 nges in the CD spectrum following removal of PHF by centrifugation suggest that PHF-tau possesses a h

175 quantitative assays to establish solvents of PHF.

176 In TBS the CD spectrum of PHF was observed to have a spectral pattern consistent w

177 does not affect the phosphorylation state of PHF and complete dephosphorylation of PHF with hydrofluo

178 tes the self-assembly of tau into tangles of PHF and straight filaments by neutralizing the inhibitor

179 each of the six tau isoforms into tangles of PHF and straight filaments, and the microtubule binding

180 d Lys-353, suggesting that ubiquitination of PHF-Tau may be an earlier pathological event than previo

181 asitism, and facilitate our understanding of PHF pathogenesis.

182 s from the assemblies formed by a variety of PHF/tau-related peptide constructs containing the motifs

183 au isoform (K19) that represents the core of PHFs.

184 cantly contribute to hyperphosphorylation of PHFs in the C-terminus.

185 Electron microscope images of PHFs show pairs of twisted ribbons with 80 nm periodicit

186 demonstrates that the secondary structure of PHFs is polyproline II.

187 le information of the molecular structure of PHFs, as previous studies have failed to identify signs

188 d only phosphorylation dependent epitopes on PHF-tau.

189 ariant rapidly forms long and highly ordered PHFs.

190 it suggests that filamentous tau in the PHF (PHF-tau) makes a substantial contribution to the overall

191 d in vitro dephosphorylation of intact PHFs, PHFs with filamentous structure abolished by formic acid

192 d to microtubules and is believed to precede PHF assembly.

193 t the anti-CML antibody labels predominantly PHF in aggregates.

194 This is remarkable as tau-protein, PHF's primary constituent, has a high abundance of helix

195 pes in the paired helical filament proteins (PHF) found in AD brain.

196 newly developed anti-PHF mAbs that recognize PHF-tau but not autopsy-derived normal adult tau on West

197 se who were first fed PHF at 3.5 mo rejected PHF relative to CMF more than did infants exposed at you

198 ating the formation of degradation-resistant PHF tangles.

199 phosphorylated tau might prevent or reverse PHF formation in Alzheimer's disease.

200 st immediately with increasing PAD severity, PHF was, in contrast, relatively well preserved until la

201 sis are effective in completely solubilizing PHF, while a variety of denaturants are ineffective.

202 of normal brains and preparations of soluble PHF-tau as well as insoluble PHF from AD brains.

203 It was found that soluble PHF-Tau is ubiquitinated at its microtubule-binding doma

204 and glycation may play a role in stabilizing PHF aggregation leading to tangle formation in AD.

205 apidly induced transcription factors, Stat3, PHF/NF-kappa B, and others are responsible for activatio

206 hosphorylation-dependent epitopes (AT8, T3P, PHF-1, 12E8, AT6, AT18, AT30) in tau proteins.

207 e highly phosphorylated polypeptides of tau (PHF-tau), with these polypeptides expressing no exons 3

208 and more limited in their distribution than PHF-1 or AP-immunoreactive NFT.

209 etry data for ubiquitin itself indicate that PHF-Tau is modified by three polyubiquitin linkages, at

210 We now show that PHF tangles isolated from AD brains are glycosylated, wh

211 emoval of PHF by centrifugation suggest that PHF-tau possesses a higher fraction of alpha-helical str

212 These data suggest that PHF/tau-positive dystrophic neurites are a common compon

213 icrotubule assembly leading to the view that PHF formation leads to microtubule deficiency in Alzheim

214 nsformed infrared spectroscopy, we find that PHFs are comprised of alpha-helices.

215 We also find that PHFs are very stable, as judged by their high melting te

216 Electron microscope studies have shown that PHFs from CBD differ from those of AD by being wider and

217 htau becomes phosphorylated at the PHF-1 (Ser-396/404) and TAU-1/AT8 (Ser-199/202) epitopes

218 increase in tau hyperphosphorylation at the PHF-1 epitope in pre-symptomatic R6/2 mice, whereas symp

219 ve thermal transitions were observed for the PHF samples in acetate buffer and water, consistent with

220 and it suggests that filamentous tau in the PHF (PHF-tau) makes a substantial contribution to the ov

221 These mAbs include the PHF-tau specific mAb AT10 and 12 newly developed anti-PH

222 to be responsible for the maintenance of the PHF structure.

223 ted form is the major protein subunit of the PHF.

224 e deficiency in the antibody response to the PHF vaccines and the heterogeneity of E. risticii isolat

225 ess dense mass, which appeared to divide the PHFs into two protofilament-like strands.

226 cular mechanisms leading to formation of the PHFs and accumulations of proteins in IBM muscle are not

227 phorylated, using a battery of antibodies to PHF/tau, neurofilament, and beta-amyloid protein.

228 similar in the ultrastructural appearance to PHF.

229 Among infants exposed to PHF for 1 mo, those who were first fed PHF at 3.5 mo rej

230 urrently available that bind specifically to PHF-tau, these data suggest that double phosphorylation

231 12/Ser214 and Thr231/Ser235 may be unique to PHF-tau.

232 tubule density was surprisingly unrelated to PHFs (P = 0.8).

233 tructure abolished by formic acid treatment (PHF(FA)) and fetal human tau protein.

234 Remarkably, the true PHF-specific antibodies recognized peptide sequences pho

235 , they can be considered as the first "true" PHF-specific antibodies capable of distinguishing tau is

236 A field study of horses vaccinated with two PHF vaccines indicated a poor antibody response, as dete

237 Ultrastructurally, PHFs from CBD were shown to be a heterogeneous populatio

238 In vivo, PHF tau, and high and medium molecular weight neurofilam

239 a pasture in Siskiyou County, Calif., where PHF is enzootic and were maintained for several weeks in

240 n the present study, we investigated whether PHF/tau-positive dystrophic neurites are located in all

241 We studied whether PHFs released from degenerating neurons could be taken u

242 ble with AT8 antibody and later changes with PHF-1 antibody.

243 pected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects wit

244 Glutamine levels correlated with PHF-1 immunostained hyperphosphorylated tau.

245 ed from E. risticii strains from horses with PHF.

246 ocalized to NFTs and immunoprecipitated with PHF-tau, but also is one of the few proteins known to un

247 B-positive neurities do not co-localize with PHF-1 or AT8 (hyperphosphorylated tau) immunoreactive ne

248 -like cells shared phosphorylated sites with PHF-tau and fetal tau, but differed from PHF-tau in thei

249 man recombinant tau in vitro as well as with PHFs isolated from NFTs from AD brains.

250 ly one pT-P motif in tau and copurifies with PHFs, resulting in depletion of soluble Pin1 in the brai

251 e diminution in AD and its relationship with PHFs has been performed.