ライフサイエンスコーパス: misfolded

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

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

3 e dismutase 1 (SOD1), which is known to form misfolded aggregates in patients with amyotrophic latera

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

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

6 e tightly regulated to avoid accumulation of misfolded aggregates.

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

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

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

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

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

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

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

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

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

16 Welders exposed to Mn(2+) had increased misfolded alphaSyn content in their serum exosomes.

17 that a prion-like, cell-to-cell transfer of misfolded alphaSyn has been recognized in the spreading

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

19 stably expressing wild-type human alphaSyn, misfolded alphaSyn was secreted through exosomes into th

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

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

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

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

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

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

26 -dependent defects caused by accumulation of misfolded and aggregation-prone proteins.

27 Prions are composed of misfolded and multimeric forms of the normal cellular pr

28 ALS patient spinal cord, contained abundant misfolded and nonnative disulfide-cross-linked aggregate

29 F508del-CFTR is misfolded and prematurely degraded.

30 protein with an 11-18 alanine tract that is misfolded and prone to form intranuclear inclusions, whi

31 gradation of short-lived proteins, which are misfolded and regulatory proteins, but not the bulk of c

32 ains of globular particles made of partially misfolded and totally inactive proteins.

33 tein synthesis is crucial to avoid producing misfolded and/or non-functional proteins.

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

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

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

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

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

39 ion that distinguishes correctly folded from misfolded CFTR.

40 PTM changes that prevented the maturation of misfolded CFTR.

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

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

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

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

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

46 , a potentiated variant developed to resolve misfolded conformers implicated in neurodegenerative dis

47 ultures expressed mutant tau and accumulated misfolded cytoplasmic tau aggregates but exhibited no UP

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

49 Here, we reveal that misfolded endogenous proteins and the human amyloid beta

50 Misfolded endoplasmic reticulum proteins are retro-trans

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

52 han a decade has shown that they contain the misfolded forms of proteins associated with Alzheimer's,

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

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

55 ycan signal required for flagging terminally misfolded glycoproteins for ERAD.

56 mbrane proteins are degraded by proteasomes, misfolded GPI-anchored proteins are primarily degraded i

57 ave post-ER itineraries that not only shield misfolded GPI-anchored proteins during their trafficking

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

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

60 prions, composed of multichain assemblies of misfolded host-encoded prion protein (PrP), act as letha

61 Neurofibrillary tangles, formed of misfolded, hyperphosphorylated tau protein, are a pathol

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

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

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

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

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

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

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

69 Misfolded luminal endoplasmic reticulum (ER) proteins un

70 While most misfolded membrane proteins are degraded by proteasomes,

71 euronal stress including the accumulation of misfolded mHTTx1.

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

73 responses are induced by aggregates or their misfolded monomeric or oligomeric precursors remains unc

74 gical chaperones" that bind to and stabilize misfolded MP variants, some of which are now in clinical

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

76 assemble into a heterogeneous collection of misfolded multimers, ranging from soluble oligomers to i

77 ed the ability of wild-type pVHL and certain misfolded mutant versions of pVHL to bind ODD, the HIF-d

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

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

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

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

82 he most highly characterized is targeting of misfolded or aggregated proteins to degradation pathways

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

84 ity of the proteome by selectively degrading misfolded or mis-assembled proteins, but the rules that

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

86 control, rapidly identifying and destroying misfolded or otherwise aberrant proteins that may be tox

87 olding and the regulated removal of damaged, misfolded, or aggregated proteins.

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

89 oteins, depending on the localization of the misfolded part, the ER lumen (ERAD-L), the ER membrane (

90 es are involved in the efficient handover of misfolded/partially folded proteins to Hsp70 but also fu

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

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

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

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

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

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

97 fatal neurodegenerative disorders caused by misfolded prion protein in the brain.

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

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

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

101 yet the cellular pathways needed to prevent misfolded proinsulin accumulation remain incompletely un

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

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

104 The formation of misfolded protein aggregates is a hallmark of neurodegen

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

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

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

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

109 ates, but also to the mechanism by which the misfolded protein causes intracellular damage.

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

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

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

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

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

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

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

117 of physiological PrP(C) into the pathogenic misfolded protein PrP(Sc), conferring new properties to

118 coded the Clp proteases, associated with the misfolded protein response.

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

120 tive therapeutic agents targeting the toxic, misfolded protein species in disease is one promising st

121 Here, we establish that hIAPP misfolded protein stress activates HIF1alpha/PFKFB3 sign

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

123 brane permeant toxic oligomers implicated in misfolded protein stress.

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

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

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

127 Misfolded protein toxicity and failure of protein qualit

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

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

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

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

132 of target tissues to degrade regulatory and misfolded proteins (e.g., proteins damaged upon exercise

133 Misfolded proteins accumulate and can activate ER stress

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

135 -associated morbidity and mortality in which misfolded proteins accumulate in body fluids and the pla

136 protein response (UPR(mt)) is activated when misfolded proteins accumulate within mitochondria and le

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

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

139 s have higher proteasome activity to degrade misfolded proteins and are intrinsically more resistant

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

141 nomachines that actively reshape non-native, misfolded proteins and assist a wide variety of essentia

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

143 stresses that manifest as an accumulation of misfolded proteins and eventually lead to cell death.

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

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

146 binding protein, also regulated clearance of misfolded proteins and was increased by proteotoxicity-a

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

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

149 Current methods for the detection of misfolded proteins are not able to detect the whole misf

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

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

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

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

154 biogenesis in the secretory pathway, triages misfolded proteins by delivering substrates to the prote

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

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

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

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

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

160 Intracellular accumulation of misfolded proteins causes toxic proteinopathies, disease

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

162 During heat shock, Hsp70 is out-titrated by misfolded proteins derived from ongoing translation in t

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

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

165 Some misfolded proteins escape the ER and are instead selecte

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

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

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

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

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

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

172 We use this method for the detection of misfolded proteins in blood plasma of patients with vari

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

174 chaperone function and reducing the load of misfolded proteins in cells.

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

176 urodegenerative disease is the deposition of misfolded proteins in the brain.

177 Misfolded proteins in the endoplasmic reticulum (ER) act

178 Misfolded proteins in the endoplasmic reticulum (ER) are

179 Misfolded proteins in the endoplasmic reticulum (ER) are

180 Abnormally high levels of misfolded proteins in the endoplasmic reticulum (ER) lum

181 Sensing misfolded proteins in the endoplasmic reticulum (ER), ce

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

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

184 Misfolded proteins in the lumen of the endoplasmic retic

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

186 ults reveal significantly elevated levels of misfolded proteins in the two stages of MDS that are mos

187 microscopically visible deposition sites of misfolded proteins in vivo.

188 on of PZP could underlie the accumulation of misfolded proteins in vivo.

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

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

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

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

193 The intracellular accumulation of aggregated misfolded proteins is a cytopathological hallmark of neu

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

195 Accretion of misfolded proteins or depletion in calcium concentration

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

197 Toxic misfolded proteins potentially underly many neurodegener

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

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

200 d by neurodegenerative diseases suggest that misfolded proteins spread through the brain along anatom

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

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

203 However, many of the misfolded proteins that accumulate in neurodegeneration

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

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

206 The misfolded proteins that are transferred between cells ar

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

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

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

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

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

212 While misfolded proteins typically aggregate and form inclusio

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

214 tion (ERAD) is a unique mechanism to degrade misfolded proteins via complexes containing several high

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

216 ins with altered physicochemical properties (misfolded proteins).

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

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

219 ciently inhibits in vitro the aggregation of misfolded proteins, including the amyloid beta peptide (

220 est that the steady-state ER localization of misfolded proteins, observed for several disease-causing

221 in all species to aid the solubilization of misfolded proteins, protein degradation, and transport.

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

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

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

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

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

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

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

229 elated neurodegenerative disorders caused by misfolded proteins.

230 itiating and carrying out the degradation of misfolded proteins.

231 requires mechanisms to recognize and remove misfolded proteins.

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

233 cellular response to stress which results in misfolded proteins.

234 t to the well-known role of Lon in degrading misfolded proteins.

235 rotein folding and preventing aggregation of misfolded proteins.

236 which is responsible for the degradation of misfolded proteins.

237 determine the earliest cellular responses to misfolded proteins.

238 ates autophagy and enhances the clearance of misfolded proteins.

239 ociated with the accumulation of damaged and misfolded proteins.

240 bunit Rpn6, and intracellular degradation of misfolded proteins.

241 folded protein response-mediated response to misfolded proteins.

242 ondrial protein quality control by degrading misfolded proteins.

243 pendent quality control systems that degrade misfolded proteins.

244 rtner to recognize and manage aggregated and misfolded proteins.

245 gradation pathway to facilitate clearance of misfolded proteins.

246 in response to accumulation of unfolded and misfolded proteins.

247 ion into cytoplasmic foci containing soluble misfolded proteins.

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

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

250 ellular functions through the degradation of misfolded, redundant, and damaged proteins.

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

252 consequence of interactions specific to the misfolded ribozyme.

253 that caused removal of a dominant-inherited misfolded secretory protein, mucin1-frameshifted, from a

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

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

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

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

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

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

260 n of mutant SOD1 mice with higher amounts of misfolded SOD1 detected within the spinal cord.

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

262 whether CLR01 could prevent the formation of misfolded SOD1 in the G93A-SOD1 mouse model of ALS and w

263 CLR01 treatment decreased misfolded SOD1 in the spinal cord significantly.

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

265 hypothesis that MIF acts as a chaperone for misfolded SOD1 in vivo and may have further implications

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

267 ogether, these findings suggest that soluble misfolded SOD1 may be the disease driver in ALS, whereas

268 mutant SOD1 develop paralysis and accumulate misfolded SOD1 onto the cytoplasmic faces of intracellul

269 e interactomes of the mitochondrial pools of misfolded SOD1.

270 F in modulating the specific accumulation of misfolded SOD1.

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

272 s, we observed that there was a high soluble misfolded/soluble total SOD1 ratio.

273 derlying the neuronal damage caused by these misfolded species are not well-defined.

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

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

276 On stalled ribosomes, a misfolded state forms rapidly (1.5 s).

277 a direct example of a functionally competent misfolded state.

278 dysfunctions have been linked to this ApoE4 misfolded state.

279 termediates or to the presence of additional misfolded states.

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

281 ed proteins are not able to detect the whole misfolded subproteome and, moreover, are rather laboriou

282 ce with this pathway induces accumulation of misfolded subunits of electron transport chain complex I

283 Misfolded tau aggregates are able to spread the patholog

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

285 , we show that the spread and propagation of misfolded tau between individual murine neurons is rapid

286 Presence of misfolded tau is not directly cytotoxic to the neuron; t

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

288 ve diseases including tauopathies, where the misfolded tau protein propagates pathology through conne

289 herefore, we demonstrate that seed-competent misfolded tau species do not acutely cause cell death, b

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

291 lts, resulting from myocardial deposition of misfolded transthyretin (TTR) or pre-albumin.

292 Misfolded, truncated, or mutated proteins as well as ove

293 receptor p62 facilitates the condensation of misfolded, ubiquitin-positive proteins and their degrada

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

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

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

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

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

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

300 g with calreticulin, directly interacts with misfolded ZAAT.