ライフサイエンスコーパス: misfold

1 aptamers may unfold in vivo and subsequently misfold.

2 fferent as starvation, infection, or protein misfolding.

3 nt molecular chaperone that inhibits protein misfolding.

4 assemblies that propagate by seeded protein misfolding.

5 in which he developed strategies to prevent misfolding.

6 nderappreciated factor in initiating protein misfolding.

7 neurodegenerative diseases caused by protein misfolding.

8 ion of the proteostasis network upon protein misfolding.

9 ps to avoid otherwise prevalent inter-domain misfolding.

10 enetic disease associated with wild-type TTR misfolding.

11 ism of this novel tactic of ligand-regulated misfolding.

12 lt in an increase in toxicity due to protein misfolding.

13 the propensity of alphasyn to pathologically misfold; 3) compare experiments evaluating the prion-lik

14 vage fragments differ in their propensity to misfold, a process that plays a key role in the pathogen

15 in the GAF-B domain of PDE10A induce PDE10A misfolding, a common pathological phenotype in many neur

16 Also, N-glycans attached to misfolded AAT are not required for accelerated degradati

17 's disease (AD) and other tauopathies is the misfolding, aggregation and cerebral accumulation of tau

18 rily composed of intracellular inclusions of misfolded alpha-synuclein (alpha-syn) among other protei

19 LBs are primarily composed of misfolded alpha-synuclein (aSyn), and neurofibrillary ta

20 alpha-synuclein promotes the accumulation of misfolded alpha-synuclein and causes midbrain dopaminerg

21 r, aged Hri(-/-) mice showed accumulation of misfolded alpha-synuclein in the lateral collateral path

22 However, in the context of extant misfolded alpha-synuclein, GCase activity modulates neur

23 A misfolded alpha-synuclein-enriched brain fraction from f

24 Recent studies showed that the release of misfolded alphaSN from human and rodent neurons is relev

25 n PFFs into culture medium, the formation of misfolded alphaSyn inclusions dramatically compromised t

26 The yeast prion [URE3] propagates as a misfolded amyloid form of the Ure2 protein.

27 heimer's disease (AD) is the accumulation of misfolded amyloid-beta (Abeta) peptide.

28 Aberrantly processed or mutant proteins misfold and assemble into a variety of soluble oligomers

29 an abundant brain neuronal protein that can misfold and polymerize to form toxic fibrils coalescing

30 (PD) is characterized by the accumulation of misfolded and aggregated alpha-synuclein (alpha-syn) int

31 Scrapie prion protein is a misfolded and aggregated form of PrP(C) responsible for

32 When these processes are not regulated, misfolding and accumulation of aberrant proteins can occ

33 ooked role in the propagation of tau protein misfolding and AD pathogenesis, providing a new conceptu

34 ted in the initiation and progression of tau misfolding and aggregation are largely unclear.

35 ults demonstrate that CLR01 can inhibit SOD1 misfolding and aggregation both in vitro and in vivo, bu

36 homeostasis occurring as a result of protein misfolding and aggregation contributes to the pathogenes

37 These misfolding and aggregation events are associated with th

38 s known about the factors that cause protein misfolding and aggregation in metazoans.

39 Protein misfolding and aggregation is the hallmark of numerous h

40 rative diseases that are associated with the misfolding and aggregation of alpha-synuclein, including

41 front line of protection from stress-induced misfolding and aggregation of polypeptides in most organ

42 The misfolding and aggregation of proteins leading to amyloi

43 Heat stress induces misfolding and aggregation of proteins unless they are g

44 ressive neurodegenerative disorder caused by misfolding and aggregation of the prion protein (PrP), a

45 ular structure of great interest because its misfolding and aggregation, along with changes in the se

46 athogenic mechanisms include alpha-synuclein misfolding and aggregation, mitochondrial dysfunction, i

47 nderstand the principles that govern protein misfolding and aggregation, which is a highly complex pr

48 erse prokaryotic and eukaryotic cells in tau misfolding and aggregation.

49 mains have shown an increased propensity for misfolding and aggregation.

50 ns, being a key aspect in pathogenic protein misfolding and aggregation.

51 passing to naive cells in which it templates misfolding and aggregation.

52 teostasis, by mitigating the risk of protein misfolding and aggregation.

53 e diseases characterized by aberrant protein misfolding and aggregation.

54 , particularly early events that trigger the misfolding and assembly of the otherwise soluble and sta

55 ich may limit the deleterious effects of RNH misfolding and assist in folding fidelity.

56 F) was shown to directly inhibit mutant SOD1 misfolding and binding to intracellular membranes.

57 ng pyrin and the actin cytoskeleton, protein misfolding and cellular stress, NF-kappaB dysregulation

58 nthesis at night, thereby preventing protein misfolding and ER stress.

59 This observation suggested that the misfolding and functional defects caused by the E217G mu

60 Given the many linkages between MP misfolding and human disease, we also examine some of th

61 y protecting nascent polypeptide chains from misfolding and maintain translational fidelity by involv

62 MT1A leads to a disproportionate increase in misfolding and mistrafficking of PMP22, which is likely

63 ature reporting a role of lipids in alphasyn misfolding and neurotoxicity in various synucleinopathy

64 mbled ribosomal proteins are highly prone to misfolding and often require dedicated chaperones to pre

65 verview of current methods to assess protein misfolding and pathogenicity both in vitro and in vivo.

66 e protease inhibitor alpha(1)-antitrypsin to misfolding and polymerisation within hepatocytes, causin

67 anges the protein structure and leads to its misfolding and polymerization, which cause endoplasmic r

68 oxic due to their strong ability to seed tau misfolding and propagate the pathology seen across diffe

69 These fibrils may induce further alphasyn misfolding and propagation of pathologic fibrils in a pr

70 ids drive tau-membrane association, inducing misfolding and self-assembly of the disordered tau into

71 standing of the mechanism of alpha-synuclein misfolding and the structures of the aggregates that are

72 ion, we characterized its effect on alphaSyn misfolding and transmission in experimental models of Pa

73 ts shed new light on the roles of NAs in PrP misfolding and TSEs.

74 gated N-terminal polyglutamine (polyQ) tract misfolds and forms protein aggregates characteristic of

75 toxic effects of mutant protein expression, misfolding, and aggregation.

76 established paradigms for how MP folding and misfolding are linked to the molecular etiologies of a v

77 of human disease, and therapies that target misfolding are transforming the clinical care of cystic

78 eric VWF and provides strong support for VWF misfolding as a result of some, but not all, type 2 VWD

79 In the secretory pathway, misfolded asparagine (N)-linked glycoproteins are select

80 It is unclear why alphasyn initially misfolds, but a growing body of literature suggests a cr

81 he proteostasis network directly engages the misfolded C-Pro domain itself to prevent secretion and i

82 er or not recognition and quality control of misfolded C-Pro domains is mediated by recognizing stall

83 proteostasis network differentially engages misfolded C1163R C-Proalpha2(I) and targets it for ER-as

84 nslation and proper protein folding, whereas misfolding can lead to aggregation and disease.

85 chaperones and protein folding facilitators, misfolding can occur quite frequently.

86 Rhodopsin misfolding caused by the P23H mutation is a major cause

87 Protein misfolding causes a wide spectrum of human disease, and

88 hey are composed of multichain assemblies of misfolded cellular prion protein.

89 ep mechanism by which alphaBc interacts with misfolded client proteins to prevent their aggregation.

90 ve bacteria results in a more pronounced tau misfolding compared to eukaryotic DNA.

91 rol of dNTPs improves fitness during protein misfolding conditions.

92 ycles lead back to the kinetically preferred misfolded conformation and are not observed, we estimate

93 unction because they destabilize deleterious misfolded conformations and inter-chain interactions.

94 ensitivity and specificity using the Protein Misfolding Cyclic Amplification (PMCA) assay.

95 Protein misfolding cyclic amplification (PMCA) is a technique th

96 Here we show the utility of the Protein Misfolding Cyclic Amplification (PMCA) technology as a s

97 munosorbent assay to measure NFL and protein misfolding cyclic amplification (PMCA) to detect alphaSy

98 ing-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA).

99 y, conformation stability assay, and protein-misfolding cyclic amplification, we monitored the confor

100 roteotoxicity from insufficient clearance of misfolded/damaged proteins underlies many diseases.

101 id light-chain (LC) amyloidosis is a protein misfolding disease in which the aggregation of an overex

102 ing many neurodegenerative diseases, protein misfolding diseases, diabetes, ischemic disorders, and c

103 rm encephalopathies (TSEs) and other protein misfolding diseases, TSEs can be used to understand othe

104 al of toxic proteins in a variety of protein misfolding diseases.

105 nt of potential therapeutics against protein-misfolding diseases.

106 tic interventions designed to combat protein misfolding diseases.

107 Amyloids are implicated in many protein misfolding diseases.

108 pproach to the targeted treatment of protein misfolding disorders, wherein the stabilisation of disea

109 ha3, and cytopathology, suggesting that they misfold during biosynthesis.

110 Misfolding during biosynthesis in the ER activates the u

111 ue to a toxic gain-of-function intracellular misfolding event involving a mutated myocilin olfactomed

112 ue insights into how large proteins fold and misfold, expanding our ability to predict and manipulate

113 Sec61 translocon causes reduced synthesis of misfolded forms of the yeast ABC transporter Yor1.

114 te how mammalian cells recognize and degrade misfolded GPI-anchored proteins.

115 amount of ATP used for native refolding of a misfolded group I intron ribozyme by CYT-19, a Neurospor

116 rRNA misfolding impairs the formation of 80S-like ribosomes,

117 led into oligomers composed of ~ 40 proteins misfolded in a beta-sheet conformation at the membrane s

118 roteins and refolding those that have become misfolded in the context of a crowded cytosol.

119 viously observed classic evidence of protein misfolding in mutations with severe phenotypes: differen

120 xC57BL/6 F1 thymocytes revealed that genomic misfolding in NOD mice is mediated in cis.

121 tasis networks mediate MP folding and manage misfolding in the cell.

122 tion (OxPhos) inhibitors and that ER protein misfolding increases ATP uptake from mitochondria into t

123 xperiments, we demonstrate the presence of a misfolded intermediate that competes with productive fol

124 uss on a possible physiological role of such misfolded intermediate.

125 the propensity of alphasyn to pathologically misfold into uniquely toxic fibrils with modulated prion

126 ally linked to cellular prion protein (PrPC) misfolding into abnormal conformers (PrPSc), with PrPSc

127 Rhodopsin mutation and misfolding is a common cause of autosomal dominant retin

128 Protein misfolding is a recurring phenomenon that cells must man

129 stress, but how they help counteract protein misfolding is incompletely understood.

130 , despite the general knowledge that protein misfolding is intimately associated with dysfunction and

131 in amyloidosis (AL amyloidosis) is caused by misfolded light chains that form soluble toxic aggregate

132 ted increased expression of genes located on misfolded loci in mice.

133 Misfolded luminal endoplasmic reticulum (ER) proteins un

134 However, quality control (QC) pathways for misfolded mitochondrial proteins remain poorly defined.

135 caused by the intracellular accumulation of misfolded MUC1 protein in the early secretory pathway.

136 tracellular fates of two naturally occurring misfolded N-glycosylated variants of human alpha1-antitr

137 ng TRAP, assembled ribosomes associated with misfolded nascent chains move into cytoplasmic compartme

138 Finally, we have found that GGPP-regulated misfolding occurred in detergent-solubilized Hmg2, a fea

139 This misfolding occurs via a transiently populated intermedia

140 (PD) is associated with the aggregation and misfolding of alpha-syn in dopaminergic neurons.

141 adation of Hmg2 and required for mallosteric misfolding of GGPP as studied by in vitro limited proteo

142 erol pathway intermediate GGPP, which causes misfolding of Hmg2, leading to degradation by the HRD pa

143 f prolines is important for the activity and misfolding of intrinsically disordered proteins.

144 at protects TMDs during assembly to minimize misfolding of multi-spanning membrane proteins and maint

145 Misfolding of nascent Tpi1 in response to both cadmium a

146 shock response is triggered by heat-induced misfolding of newly synthesized polypeptides, and so has

147 a neurodegenerative disease associated with misfolding of protein tau, indicating that sCJD might sh

148 derstanding of diseases that result from the misfolding of proteins including diabetes type II, Alzhe

149 e rare, neurological disorders caused by the misfolding of the cellular prion protein (PrP(C)) into c

150 ive disorders in human and animals caused by misfolding of the cellular prion protein (PrP(C)) into t

151 fatal neurodegenerative disorders caused by misfolding of the normal prion protein into an infectiou

152 ymes resulting in improper glycosylation and misfolding of viral glycoproteins.

153 ng gene transcription in response to protein misfolding, oncogenic cell proliferation, and other envi

154 d proteins en route to the native state from misfolded ones that need to be degraded.

155 s, it helps to remove damaged organelles and misfolded or aggregated proteins and has therefore been

156 n these pathways lead to the accumulation of misfolded or faulty proteins that may become insoluble a

157 Neurodegenerative diseases feature specific misfolded or misassembled proteins associated with neuro

158 the functional relationship between protein misfolding or aggregation and the cellular proteostasis

159 mation by protecting the native protein from misfolding or by targeting it for degradation, but no va

160 that lacked both chaperones, perhaps due to misfolding or instability.

161 tation is not associated with either protein misfolding or loss of function.

162 nine compounds that selectively reduced the misfolded P23H rhodopsin without an effect on the wild t

163 We propose that the E46K misfolding pathway avoids electrostatic repulsion betwee

164 y while inhibiting further transitions along misfolding pathways.

165 Amyloidoses (misfolded polypeptide accumulation) are among the most d

166 We have used misfolded prion protein (PrP*) as a model to investigate

167 imes, neuropathology, regional deposition of misfolded prion protein aggregates in the brain, and siz

168 butes to the lysosome function and regulates misfolded prion protein clearance.

169 somes and promoting lysosomal degradation of misfolded prion proteins in cancer cells.

170 ting into the sole causal disease agent, the misfolded prion.

171 n and failed to find even minimal amounts of misfolded prions providing definitive experimental evide

172 events membrane damage during ER escape of a misfolded proinsulin aggregate destined for lysosomal de

173 Cell-to-cell transmission of misfolding-prone alpha-synuclein (alpha-Syn) has emerged

174 ed to compute the folding pathways of large, misfolding-prone proteins that lie beyond the reach of e

175 Here we show that the underlying protein misfolding propagates rapidly between individual neurons

176 pathway with MLN4924 causes accumulation of misfolded protein aggregates, ultimately inducing immuno

177 in dMMR tumors, resulting in an abundance of misfolded protein aggregates.

178 bacter to maintain replication capacity when misfolded protein burden increases, such as during rapid

179 reover, peptides used as a proxy for exposed misfolded protein chains selectively bind to the purifie

180 Herein we report that PKR regulates misfolded protein clearance by preventing it release thr

181 gets Abeta and tau concurrently by mimicking misfolded protein clearance mechanisms of immunotherapy,

182 tein kinase R (PKR) and its association with misfolded protein expression in cancer cells are unclear

183 through the brain in a prion-like fashion by misfolded protein forming a template for aggregation of

184 maging strategy, that they can differentiate misfolded protein oligomers and insoluble aggregates, bo

185 enuate global translation, thus reducing the misfolded protein overload in the ER.

186 he NSPC chaperone network robustly maintains misfolded protein solubility and stress resilience throu

187 of protein translation, can protect against misfolded protein stress and toxicities linked to Parkin

188 y PrP(Sc), a self-replicating pathologically misfolded protein that exerts toxicity predominantly in

189 that there are global effects from a single misfolded protein that extend to many clients within cha

190 y with covalently immobilized but releasable misfolded protein to obviate possible chaperone effects

191 results in autoantibodies against aggregated misfolded protein with immune complex formation and kidn

192 ization of aggregates of a model fluorescent misfolded protein, GLR103.

193 Furthermore, misfolded protein-dependent dissociation of BiP from IRE

194 Misfolded proteins accumulate and can activate ER stress

195 ANCE STATEMENT In neurodegenerative disease, misfolded proteins accumulate and overwhelm normal syste

196 In many diseases, misfolded proteins accumulate within the endoplasmic ret

197 hey act as "holdases" and buffer unfolded or misfolded proteins against aggregation in an ATP-indepen

198 ery, which can result in the accumulation of misfolded proteins and endoplasmic reticulum (ER) stress

199 -cell imaging, we find that sequestration of misfolded proteins and nascent polypeptides into two dis

200 ature with BTZ increased the accumulation of misfolded proteins and substrate load on the 26S proteas

201 te multiple misfolded proteins, and the same misfolded proteins are involved in more than one ND, mot

202 subsequent templated amplification of these misfolded proteins are involved in the onset and progres

203 by the abnormal accumulation of unfolded or misfolded proteins at the endoplasmic reticulum (ER) is

204 date a novel mechanism for the entrapment of misfolded proteins by cargo receptors and a strategy for

205 sicles that largely exclude ER residents and misfolded proteins by mechanisms that remain unresolved.

206 These findings indicate that misfolded proteins can act as ligands to activate DR5 in

207 phenomenon that cells must manage; otherwise misfolded proteins can aggregate and become toxic should

208 In cultured human cells, we find that misfolded proteins can directly engage with DR5 in the E

209 We show that misfolded proteins can stabilize CcrM by competing for l

210 In most cells, misfolded proteins coalesce in discrete aggregates at di

211 triggered by the increased concentration of misfolded proteins due to protein-destabilizing conditio

212 n a novel simple method for the detection of misfolded proteins employing a surface plasmon resonance

213 facilitate the folding of proteins or target misfolded proteins for clearance.

214 ubiquitin-protein ligases that ubiquitinate misfolded proteins for proteasomal degradation.

215 naling pathways and accelerates clearance of misfolded proteins from the cytosol.

216 of the endoplasmic reticulum, and removal of misfolded proteins from the translocon.

217 protein 70 (Hsp70) that recognizes and traps misfolded proteins in a nucleotide-dependent manner.

218 s involved in small molecule drug design for misfolded proteins in anticancer therapy.

219 Accumulation of misfolded proteins in cells exposed to As leads to endop

220 acterized by the extracellular deposition of misfolded proteins in one or more organs.

221 Misfolded proteins in the endoplasmic reticulum (ER) are

222 Misfolded proteins in the endoplasmic reticulum (ER) are

223 y and often increase the load of unfolded or misfolded proteins in the endoplasmic reticulum (ER).

224 these conditions can promote the buildup of misfolded proteins in the ER to cause ER stress, which t

225 PR, and how decisions are made to dispose of misfolded proteins in the secretory pathway.

226 memory loss due to aberrant accumulation of misfolded proteins inside and outside neurons and glial

227 The mechanisms leading to self-assembly of misfolded proteins into amyloid aggregates have been stu

228 al progeny cells to promote sequestration of misfolded proteins into protective inclusions.

229 The chaperone-mediated sequestration of misfolded proteins into specialized quality control comp

230 tive to the stress caused by accumulation of misfolded proteins or damaged organelles.

231 Accretion of misfolded proteins or depletion in calcium concentration

232 cular assembly catalyzing the degradation of misfolded proteins or proteins no longer required for fu

233 Toxic misfolded proteins potentially underly many neurodegener

234 Because Lon recognizes misfolded proteins regardless of the stress, this mechan

235 cular mechanism by which sHsps interact with misfolded proteins remain unanswered.

236 Likely, a first critical mass of misfolded proteins starts a vicious cycle of a prion-lik

237 ntracellular or extracellular aggregation of misfolded proteins such as amyloid-beta and tau in Alzhe

238 In addition, misfolded proteins that accumulate in these diseases and

239 partments and both responses are elicited by misfolded proteins that accumulate under adverse environ

240 The misfolded proteins that are transferred between cells ar

241 se it has been linked to the accumulation of misfolded proteins that ultimately causes neuronal death

242 o heat shock proteins important in degrading misfolded proteins through chaperone-assisted selective

243 epted that these chaperones work by trapping misfolded proteins to prevent their aggregation; however

244 Most quality control pathways target misfolded proteins to prevent toxic aggregation and neur

245 While misfolded proteins typically aggregate and form inclusio

246 In yeast, many misfolded proteins undergo chaperone-dependent ubiquitin

247 The actions of USP7 orthologs on misfolded proteins were found to be conserved in Drosoph

248 ins with altered physicochemical properties (misfolded proteins).

249 enotype was characterized by accumulation of misfolded proteins, activation of the unfolded protein r

250 observation that the NDs accumulate multiple misfolded proteins, and the same misfolded proteins are

251 production of incomplete, mistranslated, or misfolded proteins, squandering the energy needed for ce

252 rative diseases (NDs) is the accumulation of misfolded proteins, they share other pathogenic mechanis

253 oteins, including the selective breakdown of misfolded proteins, we investigated whether agents that

254 rocesses like DNA replication while removing misfolded proteins, which are degraded by the Lon protea

255 ystem (UPS) to facilitate the degradation of misfolded proteins, which typically safeguards cellular

256 ion into cytoplasmic foci containing soluble misfolded proteins.

257 sp104 in generating self-nucleating seeds of misfolded proteins.

258 elated neurodegenerative disorders caused by misfolded proteins.

259 itiating and carrying out the degradation of misfolded proteins.

260 requires mechanisms to recognize and remove misfolded proteins.

261 ulate turnover of short-lived, unfolded, and misfolded proteins.

262 cellular response to stress which results in misfolded proteins.

263 rotein folding and preventing aggregation of misfolded proteins.

264 ates autophagy and enhances the clearance of misfolded proteins.

265 quality control (PQC) mechanisms that manage misfolded proteins.

266 rtner to recognize and manage aggregated and misfolded proteins.

267 gradation pathway to facilitate clearance of misfolded proteins.

268 in response to accumulation of unfolded and misfolded proteins.

269 d that the disruption of this interaction by misfolded PrP oligomers may be a cause of toxicity in pr

270 nism is that ELANE mutations promote protein misfolding, resulting in endoplasmic reticulum stress an

271 psin degradation that also cleared out other misfolded rhodopsin mutant proteins.

272 consequence of interactions specific to the misfolded ribozyme.

273 homeostasis and lead to the accumulation of misfolded secretory proteins, a condition referred to as

274 formation-restricted antibodies specific for misfolded SOD1 (B8H10 and AMF7-63), we identified the in

275 We propose that the interaction between misfolded SOD1 and TRAF6 may be relevant to the etiology

276 triggers an excitation-dependent decrease in misfolded SOD1 burden and autophagy overload.

277 emonstrated in the SOD1(G93A) rat model that misfolded SOD1 exists as distinct conformers and forms d

278 r, these mice accumulated reduced amounts of misfolded SOD1 in their spinal cords, with no observed e

279 esulted in neuroprotection with reduction of misfolded SOD1 levels and significant extension of life

280 e interactomes of the mitochondrial pools of misfolded SOD1.

281 different SOD1 variants (aggregated, soluble misfolded, soluble total) and the clinical presentation

282 esis, leading to the extensive population of misfolded species that interfere with productive folding

283 a direct example of a functionally competent misfolded state.

284 termediates or to the presence of additional misfolded states.

285 Misfolded tau aggregates are able to spread the patholog

286 Compelling evidence indicates that misfolded tau aggregates are neurotoxic, producing synap

287 s (NFTs) composed of hyperphosphorylated and misfolded tau protein are a pathological hallmark of Alz

288 indings suggest that predominantly targeting misfolded tau with AV-1980R/A could represent an effecti

289 , these methods show that mutations known to misfold the isolated A1 domain increase the rate of tryp

290 acid substitutions cause local disorder and misfold the native structure of the isolated platelet GP

291 Cdc5p and cohesin prevent condensin from misfolding the RDN into an irreversibly decondensed stat

292 morbidities, such as chronic stress, protein misfolding, traumatic brain injury or other pathological

293 Finally, we found that overexpression of the misfolded variants of Ant1 induces additional cytosolic

294 Prions are composed of PrP(Sc), a misfolded version of the cellular prion protein (PrP(C))

295 human renal carcinoma cells, both expressing misfolded versions of human pVHL.

296 continuous feeding of Drosophila expressing misfolded versions of pVHL either L- or D-arginine rich

297 GGPP-dependent misfolding was still extant but occurred at a much slowe

298 by binding of a small-molecule inhibitor of misfolding we conclude that they arise from rapid exchan

299 swapping is a potential source of transient misfolding, we demonstrate that such a kinetic trap reta

300 owers the energy barrier for alpha-synuclein misfolding, while isomerase-binding to a separate, disea