ライフサイエンスコーパス: fibrillization

1 ll as toxic gains of function (increased tau fibrillization).

2 ses and in kinetic studies of self-assembly (fibrillization).

3 ll tested compounds suggesting inhibition of fibrillization.

4 rillizing proteins need to be "prepared" for fibrillization.

5 il (residues 17-21) that significantly slows fibrillization.

6 iophysical readouts for monitoring alpha-Syn fibrillization.

7 s resulted in oligomer loss and promotion of fibrillization.

8 orphisms rather than a reliable indicator of fibrillization.

9 inhibitors of alpha-Syn oligomerization and fibrillization.

10 nge may contribute to the kinetic control of fibrillization.

11 ntified as a specific inhibitor of alpha-syn fibrillization.

12 the dopamine-induced inhibition of alpha-syn fibrillization.

13 further oligomerizes to a tetramer, prior to fibrillization.

14 presence of nontoxic monomers and to prevent fibrillization.

15 bit both Abeta1-42 early oligomerization and fibrillization.

16 transiently populated during the process of fibrillization.

17 the oligomerization of Abeta but inhibit its fibrillization.

18 ctly or indirectly on Abeta and inhibits its fibrillization.

19 now studied the effect of gelsolin on Abeta fibrillization.

20 ting that disease may arise from accelerated fibrillization.

21 cal phenomena, including crystallization and fibrillization.

22 rimary nucleation process underlying amyloid fibrillization.

23 omogenates were used to seed RT-QuIC-induced fibrillization.

24 ining compact monomer that was refractory to fibrillization.

25 eeded with infectious beta-solenoid fibrils) fibrillization.

26 s known about how these molecules affect Tau fibrillization.

27 azine (ATPZ) series of compounds inhibit Tau fibrillization.

28 mers, leading to dimers that were capable of fibrillization.

29 then enter neighboring cells to seed further fibrillization.

30 tegrity of the protein and the conditions of fibrillization.

31 K18 aggregation, and R3 is critical for K19 fibrillization.

32 lized underlying principle governing amyloid fibrillization.

33 sequently leads to a substantial increase in fibrillization.

34 azine ruthenium(II) complex to monitor Abeta fibrillization.

35 the polypeptide chains during misfolding and fibrillization.

36 es, Congo red and Lacmoid, which inhibit its fibrillization.

37 loid fibrils, a subset of which also inhibit fibrillization.

38 on between a small-molecule inhibitor of tau fibrillization, 3,3'-bis(beta-hydroxyethyl)-9-ethyl-5,5'

39 a candidate small molecule inhibitor of tau fibrillization, 3-(2-hydroxyethyl)-2-[2-[[3-(2-hydroxyet

40 a hydrophobic interface can promote amyloid fibrillization, although the underlying mechanism is sti

41 for in vivo evaluation must both prevent tau fibrillization and achieve significant brain levels.

42 al modifications of synuclein that favor its fibrillization and aggregation in inclusions in neurons

43 nsight into the early stages of beta-amyloid fibrillization and can be used to enhance the understand

44 es that are both effective inhibitors of tau fibrillization and display significant brain-to-plasma e

45 chanisms underlying halpha-Syn intraneuronal fibrillization and its contribution to PD pathogenesis,

46 design of drugs that inhibit alpha-synuclein fibrillization and might arrest disease progression.

47 ng the cause and effect relationship between fibrillization and neurodegeneration.

48 r Abeta was dependent on the degree of Abeta fibrillization and on the concentration of fAbeta.

49 n play an active role in preventing aberrant fibrillization and suggest the molecular mechanism where

50 Herein, the fibrillization and toxicity of amide-to-ester mutants of

51 ing backbone amide bonds are compared to the fibrillization and toxicity of the 19-20 E-olefin Abeta

52 matic data defining factors affecting A beta fibrillization and, thus, should be valuable in the desi

53 ation may exist between the rate of in vitro fibrillization and/or oligomerization and the progressio

54 plasma and CSF, where it prevents Abeta from fibrillization, and helps to maintain it in the soluble

55 , activation energies of oligomerization and fibrillization are estimated to be 5.5 and 12.1 kCal/mol

56 y enable inhibition of one or more stages of fibrillization as a potential therapeutic strategy.

57 cules were found to interfere with Abeta1-40 fibrillization as determined by transmission electron mi

58 ntains a BRICHOS domain, which reduces Abeta fibrillization as well as neurotoxicity in vitro and in

59 uclein-deficient neurons lacked amyloid-like fibrillization, as determined by thioflavine S staining.

60 e amyloid-forming peptides leads to enriched fibrillization at an air-water interface.

61 ained via immunization are unable to prevent fibrillization at the same substoichiometric concentrati

62 ynuclein is necessary and sufficient for its fibrillization based on the following observations: 1) h

63 These data support that Abeta fibrillization begins within AD vulnerable neurons, lead

64 Studies of the in vitro fibrillization behavior of the mutant proteins suggest t

65 l domain affected not only the extent of PrP fibrillization but also its kinetics, lowering the react

66 ctic" mutation (AbetaE22G) accelerated Abeta fibrillization but decreased the abundance of nonfibrill

67 drug candidates that inhibit alpha-synuclein fibrillization but do not block its oligomerization coul

68 t not fibrillization, compounds that inhibit fibrillization but not oligomerization, and compounds th

69 ta indicate that dopamine inhibits alpha-syn fibrillization by inducing structural changes in alpha-s

70 t Asn-181) significantly reduces the rate of fibrillization by promoting intermolecular disulfide for

71 pseudophosphorylation and glycation promoted fibrillization by shifting equilibrium toward the fibril

72 We demonstrate that fibrillization can be disrupted with a new class of inhi

73 The process of Tau fibrillization can be replicated in vitro, and a number

74 mpounds that inhibit oligomerization but not fibrillization, compounds that inhibit fibrillization bu

75 Under the same fibrillization conditions, Arctic Abeta40 exhibits a hig

76 The effect of bead mass on fibrillization correlated (R(2) = 0.96) with variations

77 Fibrillization correlates with the distinct clustering o

78 proved critical for the nucleation of Sup 35 fibrillization de novo and displayed a conformation comm

79 y little is understood about its folding and fibrillization energy landscape.

80 Dopamine inhibition of alpha-syn fibrillization generated exclusively spherical oligomers

81 Several critical factors for fibrillization have been identified.

82 eracts with one of the phenylalanines during fibrillization; however, it is not known if aromatic-aro

83 es)) in prion disease and by analogy prevent fibrillization in amyloid diseases.

84 e mechanism that prevents soluble Abeta from fibrillization in biological fluids is not clear.

85 dopamine autoxidation can prevent alpha-syn fibrillization in dopaminergic neurons through a novel m

86 thenium(II) complexes for monitoring protein fibrillization in highly fluorescent media.

87 ein homologs could be attenuating halpha-Syn fibrillization in mice, and therefore, we systematically

88 s by which gyrating beads accelerate amyloid fibrillization in microtiter plate assays are unclear.

89 pharmacological approach to the role of tau fibrillization in neurodegeneration.

90 acologic and genetic modulators of alpha-Syn fibrillization in neurons.

91 o observe the initial stages of beta-amyloid fibrillization in situ.

92 igh affinity were also capable of triggering fibrillization in the absence of other inducers.

93 (SP) and that agitation is not required for fibrillization in this setting.

94 analogous to the relationship between Abeta fibrillization in vitro and familial AD.

95 each of which has been shown to promote tau fibrillization in vitro when present at high stoichiomet

96 n microscopy as a quantitative assay for tau fibrillization in vitro, the interaction between synthet

97 he amide-to-ester Abeta 1-40 mutants prevent fibrillization; in fact several exhibit hastened amyloid

98 3), The extent of Abeta fibrillization increases with peptide concentration.

99 res required for the fatty acid class of tau fibrillization inducer using recombinant full-length tau

100 asurements when conducted in the presence of fibrillization inducers has been questioned.

101 courses performed in the presence of anionic fibrillization inducers revealed that increasing concent

102 Eight potential fibrillization inhibitor compounds reported in the liter

103 It also provides a structural basis for fibrillization inhibitors.

104 During fibrillization, inhibitory DAPHs alter the folding of Su

105 candidates that reduce amyloid 1-42 peptide fibrillization interact with the most neurotoxic species

106 It is likely that oligomeric fibrillization intermediates (protofibrils), rather than

107 There is mounting evidence that fibrillization intermediates, or protofibrils, but not m

108 Tau fibrillization is a potential therapeutic target for Alz

109 ow the rate of superoxide dismutase-1 (SOD1) fibrillization is affected by 12 different beads with a

110 Importantly, while not required for LLPS, fibrillization is enhanced in protein-rich droplets.

111 emonstrated that alpha-synuclein (alpha-syn) fibrillization is inhibited by dopamine, and studies to

112 Amyloid fibrillization is multistep process involving soluble ol

113 on with fibrillization rate, suggesting that fibrillization is not necessary for synuclein-induced ye

114 fibrillize under native conditions and that fibrillization is promoted by two solvent-exposed patche

115 This TFE-induced fibrillization is quite unusual, because most amyloidoge

116 cause of insulin's inhibitory effect on IAPP fibrillization, it has been suggested that insulin may a

117 Using fibrillization kinetics and chemical stability assays, w

118 The fibrillization kinetics depended on peptide and TFE conc

119 ble to describe the classic types of amyloid fibrillization kinetics identified in our literature sur

120 stent with the documented differences in the fibrillization kinetics of the two mutants.

121 stacked beta-sheet-seeded solutions lead to fibrillization kinetics similar to homogeneously seeded

122 The fibrillization leads to reduced adsorption of Abeta42 to

123 Inhibition of fibrillization leads to the accumulation of nonfibrillar

124 2), The onset of fibrillization limits the concentration of oligomers in

125 Both inducer micellization and tau fibrillization made significant contributions to light s

126 ibility that the toxicity of alpha-synuclein fibrillization may derive from an oligomeric intermediat

127 lt in neuronal damage, and inhibitors of Tau fibrillization may hold promise as therapeutic agents.

128 gregation through intermediate formation and fibrillization may underlie the activity of other induce

129 We uncovered two fibrillization mechanisms that govern the structural con

130 ules that prevent tau oligomerization and/or fibrillization might have therapeutic value.

131 Neither the mechanism of alpha-syn fibrillization nor the degradative process for alpha-syn

132 Further-more, the aggressive fibrillization of a C179S mutant of this fragment highli

133 The fibrillization of a truncated tau fragment that contains

134 e that apoE promotes both the deposition and fibrillization of Abeta, ultimately affecting clearance

135 vitro experiments that revealed tau-mediated fibrillization of alpha-synuclein protein at low concent

136 ired for inclusion formation and follows the fibrillization of alpha-synuclein.

137 the assay was demonstrated by following the fibrillization of beta-amyloid peptide 1-42 (Abeta42) as

138 B) the fibrillization of endogenous fibronectin is partially ha

139 o form filaments, and these peptides promote fibrillization of full-length human alpha-synuclein in v

140 In vitro, fibrillization of full-length, unphosphorylated recombin

141 arker of fluid-phase endocytosis, and induce fibrillization of intracellular full-length Tau.

142 Internalized Tau aggregates induce fibrillization of intracellular Tau in these naive recip

143 hanisms involved in the self-association and fibrillization of monomeric soluble proteins into insolu

144 The fibrillization of monomeric Tau to filaments is a multis

145 The fibrillization of mouse alpha-synuclein is slowed by WT

146 Here, we examine the role of this segment in fibrillization of PrP23-144 using a deletion variant, De

147 Fibrillization of purified recombinant alpha-synuclein i

148 elated anionic detergents greatly accelerate fibrillization of recombinant alpha-synuclein at low mic

149 To address this issue, the fibrillization of recombinant full-length four-repeat hu

150 T-QuIC) test, which is based on prion-seeded fibrillization of recombinant prion protein (rPrPSen), i

151 ic prion protein conversion prevent in vitro fibrillization of recombinant prion protein, suggesting

152 In vitro, fibrillization of recombinant tau can be induced by trea

153 h gelsolin showed that gelsolin inhibits the fibrillization of synthetic Abeta 1-40 and Abeta 1-42 at

154 s that hyperphosphorylation, misfolding, and fibrillization of tau impair synaptic plasticity and cau

155 Fibrillization of tau protein is a hallmark lesion in Al

156 gnificantly more effective at preventing the fibrillization of tau than the Abeta(1-42) peptide which

157 This mechanism is analogous to the fibrillization of the Abeta(1-42) peptide and may be imp

158 Fibrillization of the Abeta1-40 peptide under similar co

159 observations suggest that the nucleation and fibrillization of the PAPf39 peptide are a tug-of-war be

160 rils were found to be able to cross-seed the fibrillization of the parent protein, although these rea

161 conformational changes that occurred during fibrillization of the pathologic form of Htt-exon1 (NtQ4

162 ation can be reproduced in vitro in a seeded fibrillization of the recombinant prion protein variant

163 sity, can be reproduced in vitro in a seeded fibrillization of the recombinant prion protein variant

164 rriers, can be reproduced in vitro in seeded fibrillization of the Y145Stop prion protein variant.

165 that Hsp31 is able to suppress the in vitro fibrillization or aggregation of alphaSyn, citrate synth

166 cause they impair tau functions, promote tau fibrillization, or perturb tau gene splicing, thereby le

167 were attained, the rate-limiting step in the fibrillization pathway was tau dimer formation.

168 oligomers are obligate intermediates in the fibrillization pathway, we characterized the mechanism o

169 Fibrillization proceeded after intermediate formation wi

170 Thermodynamic signatures of this enhanced fibrillization process from our simulations are in good

171 but unchanged vibrational spectra during the fibrillization process suggests that a cooperative confo

172 cal cross-linking) significantly hampers the fibrillization process.

173 ld be exploited in the dissection of protein fibrillization processes as well as in the therapeutics

174 ns could be used to ascertain their relative fibrillization propensities.

175 t temperatures simulated, the results on the fibrillization propensity of the seven short de novo des

176 ed the secondary structure, aggregation, and fibrillization properties of the two Abeta40 variants an

177 uence cause different disease phenotypes and fibrillization properties.

178 eet conformation and the fastest aggregation/fibrillization properties.

179 of each bead and that bead's effect on SOD1 fibrillization rate was with regard to bead mass.

180 rease in the lag time and an increase in the fibrillization rate, consistent with promotion of both f

181 s measured, and we found no correlation with fibrillization rate, suggesting that fibrillization is n

182 cular basis for why Abeta42 exhibits greater fibrillization rates than Abeta40.

183 sease, suggesting it participates in the tau fibrillization reaction pathway.

184 qualitatively reproducing all aspects of the fibrillization reaction.

185 Induction of measurable tau fibrillization required an alkyl chain length of at leas

186 uld also be peracetylated with aspirin after fibrillization, resulting in supercharged fibrils, with

187 d levels, HSA inhibits the kinetics of Abeta fibrillization, significantly increasing the lag time an

188 nique model system in which to study protein fibrillization, since its three disulfide bridges are re

189 n was achieved concomitant with promotion of fibrillization, suggesting that oligomer and fibril form

190 Our results suggest that the fibrillization temperature (temperature above which fibr

191 bril stability and that by rank ordering the fibrillization temperatures of various sequences, PRIME2

192 e a model for Cu(II) binding to Abeta during fibrillization that is independent of peptide oligomeric

193 celles or vesicles can serve to nucleate tau fibrillization, that this mechanism underlies the activi

194 sicles can serve to nucleate alpha-synuclein fibrillization, that this mechanism underlies the induce

195 act of posttranslational modification on tau fibrillization, the ability of recombinant full-length f

196 off-pathway aggregation relative to amyloid fibrillization; these include non-linear semilog plots o

197 (1:1 ratio) collected as a function of Abeta fibrillization time, which indicates that the Cu(II) env

198 eneration link alpha-Syn oligomerization and fibrillization to the onset and progression of PD.

199 stingly, methylene blue, an inhibitor of Tau fibrillization under evaluation in Alzheimer disease cli

200 hrough which anionic surfactants promote tau fibrillization using a combination of electron microscop

201 ive assay of anionic micelle-induced protein fibrillization was characterized using tau protein, the

202 The fibrillization was reversible, and the dissociation reac

203 To this end, the kinetics of PAPf39 peptide fibrillization was studied using a battery of biophysica

204 alpha-synuclein can directly cross-seed tau fibrillization, we administered preformed alpha-synuclei

205 amyloidogenic oligomerization and contingent fibrillization were abolished.

206 "Refolding" and fibrillization were initiated by rapid dilution into pho

207 , reaction progress curves for wild-type tau fibrillization were sigmoidal and correlated well with m

208 , calpain-cleaved soluble alpha-syn inhibits fibrillization, whereas calpain-cleaved fibrillar alpha-

209 phorylation at serine 26 (S26) impairs Abeta fibrillization while stabilizing its monomers and nontox

210 The addition of anionic inducers led to fibrillization with nucleation-dependent kinetics.

211 hosphatidylserine vesicles, also induced tau fibrillization with resultant filaments originating from

212 lipid vesicles, also induced alpha-synuclein fibrillization, with resultant filaments originating fro

213 raneuronal onset of Abeta42 accumulation and fibrillization within cell bodies, neurites, and synapse