ライフサイエンスコーパス: misfolded

1 follows a seeding-nucleation model, where a misfolded aggregate or 'seed' promotes the rapid misfold

2 tients with type 2 diabetes (T2D) accumulate misfolded aggregates composed of the islet amyloid polyp

3 that PINK1 recruits Parkin proximal to focal misfolded aggregates of the mitochondrial-localized muta

4 es from a "donor cell" that is the source of misfolded aggregates to an "acceptor cell" in which misf

5 elling evidence supports the hypothesis that misfolded alpha-syn transmits from neuron-to-neuron and

6 The notion that prion-like spreading of misfolded alpha-synuclein (alpha-SYN) causes Parkinson's

7 Cell-to-cell spreading of misfolded alpha-synuclein (alpha-syn) is suggested to co

8 aggregates, which are primarily composed of misfolded alpha-synuclein (alpha-syn).

9 Misfolded alpha-synuclein (alphaS) is hypothesized to sp

10 Misfolded alpha-synuclein (AS) and other neurodegenerati

11 In Parkinson's disease, misfolded alpha-synuclein accumulates, often in a ubiqui

12 Misfolded alpha-synuclein aggregations in the form of Le

13 We conclude that misfolded alpha-synuclein can increase SOD1 aggregation

14 Parkinson's disease (PD) patients accumulate misfolded alpha-synuclein in LBs, the diagnostic signatu

15 It is known that misfolded alpha-synuclein is a key driver in PD pathogen

16 Misfolded alpha-synuclein is a key factor in the pathoge

17 mulate intracytoplasmic inclusions formed by misfolded alpha-synuclein known as Lewy bodies (LBs).

18 cts downstream of Grp94 to further recognize misfolded alpha1 subunits in a glycan-dependent manner.

19 This delivers misfolded alpha1 subunits to the Hrd1-mediated ubiquitin

20 to interfere with aggregation of particular misfolded amyloid peptides or proteins.

21 ivity wherein these MDPs specifically target misfolded amyloid seeds to inhibit IAPP misfolding which

22 Alzheimer's disease (AD) is accumulation of misfolded amyloid-beta peptides and hyperphosphorylated

23 aducanumab (a monoclonal antibody targeting misfolded amyloid-beta peptides), revitalizing the "amyl

24 own to yield qualitatively different, highly misfolded amyloid-like fibrils.

25 in postmortem brains by the presence of key misfolded and aggregated disease proteins, but cellular

26 Misfolded and aggregated forms of tau produce pathologic

27 Misfolded and aggregated forms of the prion protein (PrP

28 Misfolded and aggregated proteins bind to pattern recogn

29 70 chaperones and the Hsp104 disaggregase to misfolded and aggregated proteins during aging, but not

30 Clearance of misfolded and aggregated proteins is central to cell sur

31 ic structure of SOD1, and plaques containing misfolded and aggregated SOD1 have been found in the mot

32 ization of the folded state and formation of misfolded and aggregated species.

33 expression of HTM1 causes glycan trimming on misfolded and folded proteins, but only degradation of t

34 perone activity: TruB binds and unfolds both misfolded and folded tRNAs thereby providing misfolded t

35 tions: properly folded and non-infectious or misfolded and infectious.

36 vely sort biosynthetic cargo from diffusible misfolded and resident ER proteins.

37 R (F508del-CFTR) generates a protein that is misfolded and retained in the endoplasmic reticulum.

38 The [PSI(+)] yeast prion, which is the misfolded and self-propagating form of the translation t

39 agents that specifically bind and neutralize misfolded and toxic superoxide dismutase 1 (SOD1) mutant

40 These mutant proteins are misfolded and turnover studies show that they are ultima

41 Our observations point to misfolded Bax states, shedding light on the molecular me

42 nsights into how cells handle and respond to misfolded Cav1.

43 composed of self-propagating assemblies of a misfolded cellular protein that encode information, gene

44 p.Phe508del, results in the production of a misfolded CFTR protein, which has residual channel activ

45 hich is attributed to the degradation of the misfolded channel at the endoplasmic reticulum (ER).

46 How the misfolded client is subsequently released from BiP so th

47 iate ERAD, ADP-BiP is often recruited to the misfolded client, rendering it soluble and translocation

48 the nonglycosylated transthyretin (TTR) D18G misfolded client.

49 n, CBZ application stimulated proteolysis of misfolded collagen X by either autophagy or proteasomal

50 oss is not clear, but could be the result of misfolded complex I generating a 'non-self' response, an

51 tructural transitions between a native and a misfolded conformation and simulate their synthesis by t

52 rystallin monomers, we captured an anomalous misfolded conformation in which the beta1 and beta2 stra

53 The self-propagation of misfolded conformations of tau underlies neurodegenerati

54 ower of force spectroscopy at capturing rare misfolded conformations with potential implications for

55 iates, decreasing the likelihood of sampling misfolded conformations.

56 ional selection step, proteins often display misfolded conformations.

57 g disease (CWD) relies on immunodetection of misfolded CWD prion protein (PrP(CWD)) by western blotti

58 es in late endosomes in cells expressing the misfolded cystic fibrosis transmembrane conductance regu

59 In contrast, Nrf2 sequestered misfolded diffuse LRRK2 into more insoluble and homogene

60 Aggregation of misfolded disease-related proteins is a hallmark of neur

61 ndings can be rationalized if the folded and misfolded domains are part of the same folding funnel, w

62 Proteins with misfolded domains in the endoplasmic reticulum lumen or

63 aggregated reporter polypeptides as well as misfolded endogenous proteins inside mitochondria takes

64 Misfolded endoplasmic reticulum proteins are retro-trans

65 sult from F240 recognition of gp41 stumps or misfolded Env variants present on virions rather than it

66 ulum-associated degradation (ERAD), by which misfolded ER proteins are ubiquitinated and degraded.

67 serve as a clinical example of the effect of misfolded ER proteins retrotranslocated through the memb

68 ed alpha-syn isoforms, a potential means for misfolded extracellular or lumenal alpha-syn to access c

69 versing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfol

70 rafts in which conversion to the pathogenic misfolded form is believed to occur.

71 the peculiarity of the pathogen, which is a misfolded form of a normal protein.

72 es, characterized by the accumulation of the misfolded form of the prion protein, which is followed b

73 the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secret

74 tors and identify diagnostic markers for the misfolded forms identified here.

75 rent location, were treated with infectious, misfolded forms of the prion protein, PrP(res) We show t

76 hat this growth defect may be due in part to misfolded FtsN.

77 Misfolded glycophosphatidylinositol-anchored proteins (G

78 ns remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes fo

79 -acetylglucosamine residues (Man7GlcNAc2) on misfolded glycoproteins to facilitate their disposal.

80 ol checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with

81 0 plays an important role during ERAD of the misfolded glycosylated client null Hong Kong (NHK).

82 Here we analyzed the degradation of the misfolded GPI-AP Gas1* in yeast.

83 TRC8 also mediates degradation of the misfolded hERG-G601S disease mutant, but pharmacological

84 plicating the challenges of neuroprotection, misfolded human disease proteins and mitochondria can mo

85 Here we used a misfolded huntingtin exon I containing a 103-polyglutami

86 Here, we examined how misfolded IAPP affects Abeta aggregation and AD patholog

87 Our underlying hypothesis is that misfolded IAPP produced in T2D potentiates AD pathology

88 to be the first structural model of an ApoE4 misfolded intermediate state, which may serve to elucida

89 ve identified a structural model of an ApoE4 misfolded intermediate state.

90 of ApoE4 by preventing the formation of the misfolded intermediate state.

91 represent a conformational signature of the misfolded intermediates of amyloidogenesis and a potenti

92 protein folding, where partial unfolding of misfolded intermediates plays a key role.

93 ability of the domains present in folded and misfolded intermediates.

94 lational protein folding by helping to avoid misfolded intermediates.

95 ild-type rabbit recombinant PrP could not be misfolded into a protease-resistant self-propagating iso

96 on is attributed to PrP-scrapie (PrP(Sc)), a misfolded isoform of prion protein (PrP(C)) that accumul

97 hies, characterized by the accumulation of a misfolded isoform of the host cellular prion protein (Pr

98 Its misfolded isoform PrP(Sc) is the causative agent of prio

99 usually small plasma cell clone producing a misfolded light chain that deposits in tissues.

100 inery can accomplish retrotranslocation of a misfolded luminal protein domain across a lipid bilayer,

101 euronal stress including the accumulation of misfolded mHTTx1.

102 s range from various types of aggregates to "misfolded" monomers.

103 Stabilization of misfolded mutant beta-glucocerebrosidase (GCase) represe

104 Thus, rapid degradation of this large misfolded mutant protein in mouse retina caused little d

105 ed chains and identified mitotic regulators, misfolded nascent polypeptides, and pathological Hunting

106 lity of neuronal cells to different types of misfolded oligomeric assemblies is directly related to t

107 viding a direct link between the presence of misfolded oligomers and neuron death.

108 control (PQC) is a critical process wherein misfolded or damaged proteins are cleared from the cell

109 n conjunction with the proteasome to degrade misfolded or damaged proteins.

110 membrane proteins and secretory proteins are misfolded or incompletely folded, they are retained in t

111 olding in the organelle, the accumulation of misfolded or unfolded proteins - known as endoplasmic re

112 A misfolded, pathogenic isoform, denoted as prion, is rela

113 ultiple quality control pathways that target misfolded plasma membrane proteins, aggregated polypepti

114 n internal chamber where newly translated or misfolded polypeptides can fold to their native structur

115 ing functional alternatively folded or toxic misfolded polypeptides into harmless protease-degradable

116 ro-translocation channel for the movement of misfolded polypeptides through the endoplasmic reticulum

117 nerative diseases result from aggregation of misfolded polypeptides to form amyloids.

118 Notably, a homogeneous peptide that mimics a misfolded PQC substrate was developed and enabled quanti

119 ) may be due to cell-to-cell transmission of misfolded preformed fibrils (PFF) of alpha-synuclein (al

120 mporal relationship between the transport of misfolded prion protein (PrP(Sc)) from the brain to the

121 Prions are composed of the misfolded prion protein (PrP(Sc)) organized in a variety

122 Misfolded prion protein (PrP) seeds were observed widesp

123 egeneration, which instead results only when misfolded prion protein accompanies a specific innate im

124 Misfolded prion protein aggregates (PrP(Sc)) show remark

125 Therefore, accumulation of misfolded prion protein alone does not define targeting

126 enciphered in distinct conformations of the misfolded prion protein PrP(Sc) This concept is largely

127 Prions are unconventional agents composed of misfolded prion protein that cause fatal neurodegenerati

128 n (ERAD) is responsible for the clearance of misfolded pro-arginine vasopressin (proAVP) in the ER.

129 rs caused by prions, which are composed of a misfolded protein (PrP(Sc)) that self-propagates in the

130 A central hypothesis is that misfolded protein accumulation, spread, and distribution

131 oteasome system (UPS) to avoid a build-up of misfolded protein aggregates.

132 In contrast to other in vitro misfolded protein amplification assays-such as protein m

133 The development and adaption of in vitro misfolded protein amplification systems has been a major

134 IRE1, a component of the UPR, senses misfolded protein and cleaves XBP1 mRNA, which is ligate

135 pathway senses influenza HA as "nonself" or misfolded protein and sorts HA to ERAD for degradation,

136 urodegenerative diseases are associated with misfolded protein assemblies called amyloid.

137 e recognized as nonself by immune receptors, misfolded protein assemblies evade detection, as they ar

138 whelm ER protein quality control, leading to misfolded protein buildup, causing ER stress.

139 The pathological hallmark of misfolded protein diseases and aging is the accumulation

140 n, we provide evidence for the mechanisms of misfolded protein maturation and propagation and the eff

141 o decrease the intracellular accumulation of misfolded protein may be successful in some patients wit

142 Expression in Arabidopsis of the misfolded protein mimics zeolin or a mutated form of car

143 Misfolded protein oligomers formed during the process of

144 In factory cells, the accumulation of misfolded protein provokes the unfolded protein response

145 ghly sensitive assay system for detection of misfolded protein seeds in a murine model of prion disea

146 ntly, neither time of exposure nor amount of misfolded protein seeds present determined regions of ne

147 so provide a basis for understanding how the misfolded protein structure impacts the disease.

148 tin ligases append polyubiquitin chains onto misfolded protein substrates signaling for their degrada

149 29) mutation to glutamate or arginine led to misfolded protein that was degraded in vivo Mutation to

150 The first was the identification of a misfolded protein with transmissible properties associat

151 id receptor and degradation of a permanently misfolded protein, two previously defined roles for Sse1

152 ion machinery, or because of toxicity of the misfolded protein.

153 itro under stress conditions, including when misfolded proteins accumulate.

154 bacterial entry into the cytosol results in misfolded proteins accumulating at the bacterial membran

155 across many neurodegenerative diseases, with misfolded proteins acting as seeds for "prion-like" conv

156 ing mechanisms to reduce the accumulation of misfolded proteins an attractive therapeutic strategy.

157 le-dependent inclusion bodies that sequester misfolded proteins and are ultimately removed by autopha

158 halose in studies of autophagic clearance of misfolded proteins and for targeting SGs as a possible t

159 The toxicity of misfolded proteins and mitochondrial dysfunction are piv

160 ins that can reduce the cellular toxicity of misfolded proteins and prevent neurodegeneration.

161 Misfolded proteins are associated with many human diseas

162 Importantly, misfolded proteins are not targeted for degradation by t

163 in misfolding or facilitate the clearance of misfolded proteins are predicted to slow disease progres

164 COPII-coated vesicles, whereas resident and misfolded proteins are substantially excluded from vesic

165 The present study shows that misfolded proteins are ubiquitinylated, suggesting that

166 racterized pathologically by accumulation of misfolded proteins as a result of gene mutations or abno

167 characterized by extracellular deposition of misfolded proteins as insoluble fibrils.

168 ew the proposed mechanisms whereby exemplary misfolded proteins associate with mitochondria and their

169 Misfolded proteins associate with mitochondria, forming

170 k2 facilitates vacuole-mediated clearance of misfolded proteins by promoting inclusion body formation

171 teostasis by supporting the removal of toxic misfolded proteins by proteasomal degradation.

172 neddylation and promotes the degradation of misfolded proteins by the proteasome.

173 for the degradation of chaperone-associated misfolded proteins by the ubiquitin-proteasome system.

174 Persistent accumulation of misfolded proteins causes endoplasmic reticulum (ER) str

175 ave been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and

176 uring development as well as many neurotoxic misfolded proteins during pathogenesis.

177 sis by selectively recognizing and targeting misfolded proteins for degradation.

178 ated polypeptides and cytosolic heat-induced misfolded proteins for degradation.

179 quality control mechanisms target terminally misfolded proteins for ER-associated degradation (ERAD).

180 Misfolded proteins form aggregates containing ubiquitin-

181 regulatory proteins and removes damaged and misfolded proteins from cells.

182 ocalizes on polarized mitochondria harboring misfolded proteins in foci with ubiquitin, optineurin, a

183 ses are characterized by the accumulation of misfolded proteins in intra- and extracellular inclusion

184 tion in vitro, prevented the accumulation of misfolded proteins in living cells, and reduced the cyto

185 The aggregation of misfolded proteins in the brain occurs in several neurod

186 ns involving the deposition of assemblies of misfolded proteins in the brain, insights are now being

187 xidative stress and aberrant accumulation of misfolded proteins in the cytosol are key pathological f

188 thway facilitates the disposal of terminally misfolded proteins in the early secretory pathway yet sp

189 Accumulation of misfolded proteins in the endoplasmic reticulum (ER) cau

190 is protective against toxic accumulations of misfolded proteins in the endoplasmic reticulum, but is

191 ate damage by preventing the accumulation of misfolded proteins in the endoplasmic reticulum.

192 To minimize the accumulation of misfolded proteins in the ER, a protein quality control

193 culum (ER) stress causes the accumulation of misfolded proteins in the ER, activating the transcripti

194 which protects cells against accumulation of misfolded proteins in the ER, is induced in several age-

195 stress is brought on by the accumulation of misfolded proteins in the ER, which leads to activation

196 lum (ER) localized endonuclease activated by misfolded proteins in the ER.

197 a result of the accumulation of unfolded or misfolded proteins in the ER.

198 Soon thereafter, a distinct UPRmt induced by misfolded proteins in the mitochondrial intermembrane sp

199 nvolve the damaging accumulation of specific misfolded proteins in thread-like aggregates.

200 e ubiquitin proteasome system (UPS) degrades misfolded proteins including those implicated in neurode

201 An example is the self-assembly of misfolded proteins into amyloid fibrils, which is relate

202 cytosolic Hsp70s leads to enhanced entry of misfolded proteins into mitochondria and elevated mitoch

203 Antibody therapy targeting misfolded proteins is a potential new therapy for the ma

204 for this pathway, and the failure to destroy misfolded proteins is associated with a number of human

205 Elimination of misfolded proteins is crucial for proteostasis and to pr

206 se, the toxic accumulation of aggregates and misfolded proteins is often accompanied with widespread

207 In eukaryotic cells, the removal of misfolded proteins is primarily accomplished by the ubiq

208 integral part of the cellular management of misfolded proteins is their spatial sequestration into s

209 but whether this modification is specific to misfolded proteins is unknown.

210 diseases where disease-related assemblies of misfolded proteins might also be present in urine.

211 Misfolded proteins of the ER are retrotranslocated to th

212 expression of chaperones that refold damaged misfolded proteins or facilitate their degradation.

213 ndoplasmic reticulum (ER) stress occurs when misfolded proteins overwhelm the capacity of the ER, res

214 Misfolded proteins represent an important class of subst

215 stress increases capacity for degradation of misfolded proteins retained in the ER.

216 ecPMCA) generated different self-propagating misfolded proteins spontaneously.

217 nes similarly to the aggregation of toxic or misfolded proteins such as those associated with Parkins

218 for the proteasomal degradation of cytosolic misfolded proteins targeted by Rsp5 after heat-shock (HS

219 s binding Nt-Arg and other N-degrons.Soluble misfolded proteins that fail to be degraded by the ubiqu

220 sease mechanism involving the interaction of misfolded proteins through cross-seeding events which ma

221 stem monitors protein folding and eliminates misfolded proteins through either ER-associated protein

222 on of J-domains of transferring unfolded and misfolded proteins to Hsp70.

223 ms to enhance the folding and degradation of misfolded proteins to restore proteostasis.

224 Accumulation of misfolded proteins triggers endoplasmic reticulum stress

225 ust be achieved between the rapid removal of misfolded proteins versus providing sufficient time for

226 AD) machinery efficiently targets terminally misfolded proteins while avoiding the misidentification

227 se activity, which is required for refolding misfolded proteins while coping with ER stress.

228 which uses EVs as vehicles for immature and misfolded proteins, forming circulating immune complexes

229 acid analogues, or the ectopic expression of misfolded proteins, induce protein misfolding.

230 esponse to the accumulation of aggregates of misfolded proteins, known as aggresomes.

231 pe with stress and increased accumulation of misfolded proteins, plants and animals use a survival pa

232 on of diverse molecular architectures by the misfolded proteins, variants referred to as proteopathic

233 amyloidosis is caused by the accumulation of misfolded proteins, which induces the dysfunction of vit

234 ionally, it degrades abnormal/damaged/mutant/misfolded proteins, which serves a quality-control funct

235 ies are characterized by the accumulation of misfolded proteins, which ultimately interfere with norm

236 ER in DYT1 mice by increasing the amount of misfolded proteins.

237 drome, which arise from transport defects of misfolded proteins.

238 , which aid in the clearance or refolding of misfolded proteins.

239 ide a powerful strategy for the clearance of misfolded proteins.

240 allow for the degradation of aggregated and misfolded proteins.

241 n4 induces TMC1 transcription in response to misfolded proteins.

242 001 is a monoclonal antibody targeting these misfolded proteins.

243 thereby enables refolding or degradation of misfolded proteins.

244 ated distinct mechanisms to handle different misfolded proteins.

245 other diseases involving the accumulation of misfolded proteins.

246 ch defects are caused by the accumulation of misfolded proteins.

247 12 has been shown to facilitate clearance of misfolded proteins.

248 romoting ER-associated degradation (ERAD) of misfolded proteins.

249 tress-induced degradation and aggregation of misfolded proteins.

250 have developed stress responses to deal with misfolded proteins.

251 ght control of partitioning and recycling of misfolded proteins.

252 n the prion protein gene and accumulation of misfolded PrP with protease-resistant fragments (PrP(res

253 stingly, the proteases involved in resolving misfolded Psd1(ts) vary depending on its autocatalytic s

254 unit 13 mediated degradation specifically of misfolded R91W RPE65.

255 folding, and using these, protease-resistant misfolded recombinant rabbit PrP was generated.

256 its ClpP or ClpX induces the accumulation of misfolded SDHB, impairing oxidative phosphorylation and

257 al determinants for the efficient removal of misfolded secretory glycoproteins.

258 MDPs block amyloid seeding and directly bind misfolded, seeding-capable IAPP species.

259 teinaceous infectious agents that consist of misfolded, self-replicating states of a sialoglycoprotei

260 teinaceous infectious agents that consist of misfolded, self-replicating states of the prion protein

261 hown to directly inhibit the accumulation of misfolded SOD1 and its binding to intracellular membrane

262 ronal cultures inhibited the accumulation of misfolded SOD1 and rescued from mutant SOD1-induced cell

263 Using inhibition of misfolded SOD1 deposition onto mitochondria as an assay,

264 defense mechanism against proteotoxicity of misfolded SOD1 in the nucleus.

265 ecognizes this NES-like sequence and exports misfolded SOD1 to the cytoplasm.

266 dies against the NES-like sequence recognize misfolded SOD1, but not native wt SOD1 both in vitro and

267 We found that the accumulation of misfolded SOD1, its association with mitochondrial and E

268 em to modulate the selective accumulation of misfolded SOD1.

269 Metastable proteins tend to populate misfolded species that are prone to forming toxic aggreg

270 ing and leads to efficient ER export of even misfolded species.

271 n two biophysical properties of the client's misfolded state (M state): its stability and its kinetic

272 c)-seeded conversion of recombinant PrP to a misfolded state in an in vitro reaction (RT-QuIC).

273 dysfunctions have been linked to this ApoE4 misfolded state.

274 d a corresponding set of approximately 25000 misfolded states to illustrate the problems that can ari

275 proteins are much larger and often populate misfolded states, complicating their folding process sig

276 res, three intermediate states, and numerous misfolded states, the latter of which have not previousl

277 e domain populate ensembles of fast-forming, misfolded states.

278 by the R61T mutation in the ApoE4 native and misfolded states.

279 Their analysis is based on a partially misfolded structure of the iron-sulfur cluster domain of

280 le funnel with two folded structures and one misfolded structure that are stabilized by H-bonds.

281 e initial intermediates leading to folded or misfolded structures.

282 ns containing tandem repeats may form stable misfolded structures.

283 rmational rearrangements in order to bind to misfolded substrate proteins and prevent cellular protei

284 o increases clearance not only of terminally misfolded substrates, but also of wild-type glycoprotein

285 alosin-containing protein (VCP)/p97 extracts misfolded subunits from the endoplasmic reticulum membra

286 Unassembled and misfolded subunits undergo ER-associated degradation (ER

287 with glutamate receptor blockers attenuated misfolded tau accumulation and neuronal death.

288 Here, we show that when misfolded tau assemblies enter the cell, they can be det

289 ated that experimentally propagated forms of misfolded tau can exist as conformationally distinct "st

290 dies in cell and animal models revealed that misfolded tau can propagate from cell to cell and from r

291 ed accumulation and extracellular release of misfolded tau followed by neuronal death, which we confi

292 d within the last decade to suggest that the misfolded tau in tauopathies possesses prion-like featur

293 pathies may be a reflection of the strain of misfolded tau that propagates in each disease.

294 ctive with antibodies to 4R tau, phosphotau, misfolded tau, ubiquitin, and p62.

295 E482K is more severely misfolded than G269S, as observed by its aggregation and

296 misfolded and folded tRNAs thereby providing misfolded tRNAs a second chance at folding.

297 Nanomolar misTTR inhibits fibrillogenesis of misfolded TTR under micromolar concentrations.

298 ulum (ER) stress arises from accumulation of misfolded/unfolded proteins when protein load overwhelms

299 Rescuing misfolded versions of DAT by pharmacochaperoning is of t

300 tion of natively folded and mutation-induced misfolded von Willebrand disease (VWD) variants, we test