ライフサイエンスコーパス: polyQ

1 without polyQs) and a long (CT-long with 27 polyQs) CT fragment.

2 ent of the androgen receptor that contains a polyQ tract associated with the disease spinobulbar musc

3 mal Htt exon 1, comprising the N17 domain, a polyQ tract of 17 glutamines, and a short hexameric poly

4 which the native AR is replaced by either a polyQ AR or a polyQ AR lacking the two lysine residues t

5 n of mutant gene expression by only 50% in a polyQ disease model can have a significant impact on dis

6 ous properties of the resulting fibrils in a polyQ-independent manner.

7 The genetic expansion of a polyQ tract triggers the formation of amyloid aggregates

8 ive AR is replaced by either a polyQ AR or a polyQ AR lacking the two lysine residues that are SUMOyl

9 Using a polyQ-expanded fragment of huntingtin exon-1 (Htt103Q),

10 bution requires the mRNAs to interact with a polyQ-containing protein, Whi3, and a Pumilio protein wi

11 eviously shown an RNA-binding protein with a polyQ-expansion called Whi3 is essential for the spatial

12 n aggregation initiation mechanism for Abeta-polyQ hybrids, and by extension for full-length Abeta pe

13 scriptional function of the ligand-activated polyQ AR and indicate that the SUMOylation pathway may b

14 tent co-localization between ubiquilin-2 and polyQ aggregated proteins during disease progression in

15 nverse correlation between fibril length and polyQ repeat length, suggesting possible polyQ length-de

16 rt observed in both htt-depleted neurons and polyQ-htt-expressing neurons is correlated with ineffici

17 port for this model was provided by the anti-polyQ antibody 3B5H10, which was reported to specificall

18 , the affinity and stoichiometry of the anti-polyQ antibody MW1 increased with the number of glutamin

19 Thus, disease-associated polyQ stretches preferentially adopt compact conformatio

20 Because polyQ tracts are potential therapeutic targets for these

21 There is a widespread association between polyQ expansions and RNA-binding motifs, suggesting that

22 lso reduces interchain entanglements between polyQ domains.

23 ion of Gts1p reduced the interaction between polyQ and other prion-like proteins, and enhanced the as

24 The resulting defective clearance of both polyQ-htt aggregates and dysfunctional mitochondria by n

25 Normal AR promoted, but polyQ-AR interfered with, TFEB transactivation.

26 been proposed for amyloid fibrils formed by polyQ peptides.

27 While motor impairment mediated by polyQ-expanded HTT has been intensively studied, molecul

28 h neurodegenerative disorders induced by CAG/polyQ expansion.

29 Expansion of the CAG/polyQ region of CACNA1A occurs within alpha1ACT and lead

30 family of neurodegenerative disorders called polyQ diseases.

31 echanisms, including recruitment of cellular polyQ proteins.

32 We found that, as expected, D-polyQ monomers are not recognized by proteins that recog

33 However, amyloid fibrils prepared from D-polyQ peptides can efficiently seed the aggregation of L

34 l amyloid fibrils composed of either L- or D-polyQ peptides and found that D-fibrils are as cytotoxic

35 polyQ-Htt aggregates and robustly decreased polyQ-Htt protein abundance without concomitant cellular

36 onfirmed that they are critical in degrading polyQ proteins (expanded huntingtin exon 1) but not othe

37 brain-specific coexpression of DNAJB6 delays polyQ aggregation, relieves symptoms, and prolongs lifes

38 monomeric Httex1 proteins of five different polyQ lengths.

39 folding of Htt-exon-1 across five different polyQ-lengths.

40 Association with this discontinuous polyQ domain did not prevent 103Q aggregation, but alter

41 rofibrillary tangles in Alzheimer's disease, polyQ inclusions in expansion repeat diseases and variou

42 ement of these residues by arginine enhances polyQ AR activity as a hormone-dependent transcriptional

43 ed the full assignment of N17 and the entire polyQ tract.

44 Expanded polyQ leads to htt aggregation.

45 ragment of human huntingtin with an expanded polyQ and develop a neurological disease resembling Hunt

46 ficiently degrade Htt-exon1 with an expanded polyQ stretch both in neuronal cells and in vitro.

47 Second, an expanded polyQ tract contained multiple epitopes for fragments an

48 t polypeptide, alpha1ACT-bearing an expanded polyQ tract-lacks transcription factor function and neur

49 coil structures for both normal and expanded polyQ in the preaggregation state.

50 ing of MW1 and 3B5H10 to normal and expanded polyQ repeats within huntingtin exon 1 fusion proteins.

51 between normal and disease-causing expanded polyQ repeats of huntingtin is unknown.

52 gates formed by proteins containing expanded polyQ repeats remain poorly understood, in part due to t

53 re capable of efficiently degrading expanded polyQ sequences without an inhibitory effect on the prot

54 n a specific toxic conformation for expanded polyQ.

55 roversy regarding the processing of expanded polyQ repeats, we examined whether the proteasome can ef

56 alpha1ACT protein with a normal or expanded polyQ.

57 pathologic conformation of soluble expanded polyQ is not a valid target for drug design.

58 pathologic conformation of soluble expanded polyQ.

59 or cells and tissues expressing the expanded polyQ compared to unexpanded control.

60 ognize a single epitope specific to expanded polyQ.

61 bodies bound to normal, as well as expanded, polyQ in huntingtin exon 1 fusion proteins.

62 n by lin-18/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity

63 c systems to selectively and acutely express polyQ AR in either motor neurons (NeuroAR) or myocytes (

64 Here we expressed polyQ peptides in cells and show that their intracellula

65 sis, we generated transgenic mice expressing polyQ-expanded ataxin-7 with a second-site mutation (D26

66 e sequence ([Formula: see text]) facilitates polyQ aggregation by encouraging the formation of prefib

67 considered a possible therapeutic agent for polyQ diseases.

68 Httex1 adopts tadpole-like architectures for polyQ lengths below and above the pathological threshold

69 lts have implications for drug discovery for polyQ diseases because they suggest that the residues fl

70 This reveals a physiological function for polyQ-driven assemblies in regulating cell polarity.

71 t the aggregation free energy landscapes for polyQ peptides of different repeat-lengths.

72 results support the linear lattice model for polyQ binding proteins, suggesting that the hypothesized

73 ed huntingtin protein and peptide fragments (polyQ-Htt).

74 ciate effects of diminished AR function from polyQ-mediated proteotoxicity by enhancing the transcrip

75 es from increased prominence of the globular polyQ domain.

76 Expansion of a poly-glutamine (polyQ) repeat in a group of functionally unrelated prote

77 The presence of expanded poly-glutamine (polyQ) repeats in proteins is directly linked to the pat

78 a type 6 (SCA6) is linked to poly-glutamine (polyQ) within the C terminus (CT) of the pore-forming su

79 cated exactly in fibrils from a beta-hairpin polyQ.

80 of unique challenges: the long homopolymeric polyQ tract contains nearly identical residues, exon 1 d

81 terchain entanglements through homopolymeric polyQ and barriers to intermolecular associations appear

82 We sought to determine whether and how polyQ-expanded ataxin-7 affects SAGA catalytic activity.

83 e the diversity and sizes of the soluble Htt-polyQ aggregates that have been linked to cytotoxicity a

84 ity are unknown, we investigated soluble Htt-polyQ aggregates using analytical ultracentrifugation.

85 -2 preferentially associates with huntingtin polyQ expansion aggregates compared to alpha-synuclein,

86 in which polyglutamine-expanded huntingtin (polyQ-htt) is predominantly cleared by autophagy.

87 ells, ubiquilin-2 associates with huntingtin/polyQ aggregates, but this is not compromised by disease

88 lic enzymes) were found to rapidly hydrolyze polyQ sequences in peptides, proteins, or insoluble aggr

89 egation by chaperones should greatly improve polyQ clearance and prevent aggregate formation.

90 In polyQ disorders, synaptic dysfunction and neurodegenerat

91 hanges occurred without overt alterations in polyQ AR expression or aggregation, revealing the favora

92 The lack of chiral discrimination in polyQ amyloid cytotoxicity is consistent with several to

93 inform new strategies for neuroprotection in polyQ-expansion diseases.

94 K2-facilitated degradation of TRiC increases polyQ protein aggregation, which is involved in HD.

95 n a huntingtin exon 1 fragment of increasing polyQ lengths (HttEx1Qn), the aggregation of which is ti

96 continuous global compaction with increasing polyQ length that derives from increased prominence of t

97 We found that scyllo-inositol-induced polyQ-Htt reduction was by rescue of degradation pathway

98 s, indicating that DNAJB6 and DNAJB8 inhibit polyQ peptide aggregation directly.

99 proteins enabled us to identify interesting polyQ-length-dependent effects on Httex1 oligomer and fi

100 des with N=8 or more undergo conversion into polyQ beta-sheet aggregates.

101 The results provide insights into polyQ solution structure and fibril formation while also

102 e created tractable models for investigating polyQ toxicity in yeast cells.

103 pathogenesis in these diseases, as isolated polyQ tracts are toxic, and an N-terminal huntingtin fra

104 This activity of ataxin 3 and its polyQ-mediated interaction with beclin 1 was competed fo

105 , we studied chemically synthesized D- and L-polyQ in vitro.

106 es can efficiently seed the aggregation of L-polyQ monomers in vitro, and vice versa.

107 vely seed the aggregation of cell-produced L-polyQ proteins, suggesting a surprising lack of stereoch

108 not recognized by proteins that recognize L-polyQ monomers.

109 Large, polyQ-rich inclusions in patient brains and in cell and

110 roximate unitary n values for similar length polyQs containing beta-hairpin motifs.

111 of insoluble species of AR with a very long polyQ (Q112) tract, which typically aggregates into the

112 ract that is abrogated by a competing longer polyQ mutation in a disease protein, and identify a dele

113 nd aggregation kinetics of K2Q24K2W, a model polyQ sequence.

114 ry polyglutatmine (polyQ) motifs or modulate polyQ aggregation, indicating possible connections with

115 scyllo-inositol-induced reduction in mutant polyQ-Htt protein levels.

116 (N terminus containing 17 amino acids (N17), polyQ, and proline-rich domain (PRD)) become ordered at

117 Moreover, the contribution of non-polyQ C-terminal fragments is unknown.

118 provide structural evidence for the observed polyQ length threshold in HD pathology.

119 n host defense against toxic accumulation of polyQ proteins.

120 by enhancing the transcriptional activity of polyQ AR.

121 that influence misfolding and aggregation of polyQ disease proteins.

122 gested that Gts1p arrests the aggregation of polyQ molecules at the level of nonfibrillar species, ac

123 ecular chaperones prevent the aggregation of polyQ-containing proteins.

124 Quantitative proteomic analysis of polyQ interactors showed that expression of Gts1p reduce

125 r revealed that the supercompact behavior of polyQ is mainly due to the "glue-like" behavior of gluta

126 ing that inhibition of caspase-7 cleavage of polyQ-ataxin-7 may be a promising therapeutic strategy f

127 oth neurogenic and myogenic contributions of polyQ AR to several acute aspects of pathology and provi

128 omal degradation of mHtt-exon1 was devoid of polyQ peptides as partial cleavage products by incomplet

129 In a murine model, disruption of polyQ AR SUMOylation rescued exercise endurance and type

130 s may not accurately reproduce the effect of polyQ repeat length and solution conditions on Httex1 ag

131 onflicting evidence regarding the effects of polyQ-ATXN7 on the activity of Gcn5, the HAT catalytic s

132 chemical restriction in seeded elongation of polyQ amyloid.

133 veal a crucial role for muscle expression of polyQ-AR in SBMA and suggest muscle-directed therapies a

134 Expression of polyQ-htt in either primary neurons or striatal cells fr

135 yQ-Htt aggregates to investigate the fate of polyQ-Htt-drug complexes.

136 purified DNAJB6 can suppress fibrillation of polyQ peptides far more efficiently than polyQ expanded

137 d the interactive surfaces of toxic forms of polyQ proteins and direct them into nontoxic aggregates.

138 g an approach to the design of inhibitors of polyQ amyloid growth that focuses on conformational requ

139 odels are consistent with the involvement of polyQ aggregation in the disease mechanism.

140 regarding the thermodynamics and kinetics of polyQ folding and aggregation.

141 ce, possibly due to relatively low levels of polyQ AR expression.

142 d DNAJB8 also affected the soluble levels of polyQ peptides, indicating that DNAJB6 and DNAJB8 inhibi

143 Since reducing levels of polyQ proteins can decrease their toxicity, we tested wh

144 ese findings suggest a dominant mechanism of polyQ-mediated SAGA inhibition that potentially contribu

145 tors of the driving forces and mechanisms of polyQ aggregation in sequence segments associated with H

146 ation, and suggest that soluble oligomers of polyQ-expanded HTT are more toxic than are inclusion to

147 for unraveling early events in the onset of polyQ diseases.

148 Early prevention of polyQ aggregation by DNAJB6 occurs also in cells and lea

149 how some cellular and physical properties of polyQ amyloid vary with the chirality of the glutamine r

150 ataxia, which resulted in ~50% reduction of polyQ-ataxin-7 expression.

151 in the nucleation mechanism and structure of polyQ amyloid and have implications for the nature of th

152 However, conditional expression studies of polyQ disease models demonstrate that suppression of gen

153 OPLS-AA/L to be most suitable for studies of polyQ folding and aggregation.

154 y demonstrate that inhibiting SUMOylation of polyQ AR restores much of its transcriptional activity a

155 anism of DNAJB6 and DNAJB8 is suppression of polyQ protein aggregation by directly binding the polyQ

156 oteins were themselves potent suppressors of polyQ-expanded huntingtin exon-1 toxicity, in both yeast

157 nvestigated the effect of scyllo-inositol on polyQ-Htt accumulation.

158 observations regarding the effects of N17 on polyQ aggregation.

159 esult is consistent with our cell results on polyQ recruitment but is inconsistent with previous lite

160 similar phenomenon was also seen with other polyQ disease proteins, including mutant ataxin 3 itself

161 a conformational change above the pathogenic polyQ threshold resulting in a specific toxic conformati

162 Polyglutamine (polyQ) amyloid fibrils are observed in disease tissue an

163 Polyglutamine (polyQ) expansion of the androgen receptor (AR) causes Ke

164 Polyglutamine (polyQ) peptides are a useful model system for biophysica

165 Polyglutamine (polyQ) repeat expansion in the deubiquitinase ataxin-3 c

166 Polyglutamine (polyQ) sequences are found in a variety of proteins, and

167 untington's disease (HD) is a polyglutamine (polyQ) disease caused by aberrant expansion of the polyQ

168 e is caused by expansion of a polyglutamine (polyQ) domain within exon 1 of the huntingtin gene (Htte

169 d aggregation propensity of a polyglutamine (polyQ) expansion in exon 1 of mutant huntingtin protein

170 It is caused by a polyglutamine (polyQ) expansion in the androgen receptor (AR), a transc

171 type 7 (SCA7) is caused by a polyglutamine (polyQ) expansion in the ataxin-7 protein, categorizing S

172 enerative disease caused by a polyglutamine (polyQ) expansion in the N-terminal region of the protein

173 e is caused by expansion of a polyglutamine (polyQ) repeat in the huntingtin protein.

174 rder caused by expansion of a polyglutamine (polyQ) stretch within the Huntingtin (Htt) protein.

175 a pathological expansion of a polyglutamine (polyQ) tract in the coding region of the ATXN2 gene.

176 egenerative disease caused by polyglutamine (polyQ) expansion within the N-terminal region of the ata

177 ve disorder caused by a CAG - polyglutamine (polyQ) repeat expansion in the ataxin-7 gene.

178 SBMA is caused by CAG-polyglutamine (polyQ) repeat expansions in the androgen receptor (AR) g

179 belongs to the family of CAG/polyglutamine (polyQ)-dependent neurodegenerative disorders.

180 egates of proteins containing polyglutamine (polyQ) repeats are strongly associated with several neur

181 translated into an elongated polyglutamine (polyQ) tract in AR protein (ARpolyQ).

182 at PML deficiency exacerbates polyglutamine (polyQ) disease in a mouse model of spinocerebellar ataxi

183 number mutations that expand polyglutamine (polyQ) tracts beyond a certain threshold cause incurable

184 isorder caused by an expanded polyglutamine (polyQ) domain near the N-terminus of the huntingtin (htt

185 cular species in the expanded polyglutamine (polyQ) repeat diseases range from various types of aggre

186 isorder caused by an expanded polyglutamine (polyQ) repeat in the TATA-box-binding protein (TBP).

187 isorder caused by an expanded polyglutamine (polyQ) repeat within the protein huntingtin (Htt).

188 protein arising from expanded polyglutamine (polyQ) sequences in the exon-1 region of mutant huntingt

189 the presence of the expanded polyglutamine (polyQ) tract and are stronger in the nucleus compared wi

190 oteins containing an expanded polyglutamine (polyQ) tract are thought to initiate aggregation and tox

191 (HD) is caused by an expanded polyglutamine (polyQ) tract in the huntingtin (htt) protein.

192 tivity or bearing an expanded polyglutamine (polyQ) tract led to partially overlapping phenotypes.

193 (HTT) fragments with expanded polyglutamine (polyQ) tracts are a pathological hallmark of Huntington'

194 seases are caused by expanded polyglutamine (polyQ) tracts in different proteins, such as huntingtin

195 ion of proteins with expanded polyglutamine (polyQ) tracts is directly relevant to the formation of n

196 ion of proteins with expanded polyglutamine (polyQ) tracts.

197 protein (mHtt) with extended polyglutamine (polyQ) sequence at the N terminus leads to neuronal dege

198 inclusions immunoreactive for polyglutamine (polyQ) antibodies.

199 gion of the gene resulting in polyglutamine (polyQ) expansion which has been assumed to result in gai

200 er caused by the expansion of Polyglutamine (polyQ) in exon 1 of the Huntingtin protein.

201 conformational preferences of polyglutamine (polyQ) sequences are of major interest because of their

202 Expansions of polyglutamine (polyQ) tracts in nine different proteins cause a family

203 death after the expansion of polyglutamine (polyQ) tracts longer than approximately 40 repeats encod

204 The aggregation of polyglutamine (polyQ)-containing proteins is at the origin of nine neur

205 Expansions of preexisting polyglutamine (polyQ) tracts in at least nine different proteins cause

206 that it includes a C-terminal polyglutamine (polyQ) tract that is absent in nonrodent SRY proteins, a

207 t on the repeat length of the polyglutamine (polyQ) sequence in the disease protein.

208 an abnormal expansion in the polyglutamine (polyQ) track of the Huntingtin (HTT) protein.

209 alpha1ACT also contains the polyglutamine (polyQ) tract that, when expanded, causes spinocerebellar

210 Expansion of the polyglutamine (polyQ) tract within the androgen receptor (AR) causes ne

211 repeats encoding consecutive polyglutamines (polyQ) in the corresponding disease protein.

212 elation between the extended polyglutamines (polyQ) within exon-1 of Huntingtin protein (Htt) and age

213 Many genes carry polyglutatmine (polyQ) motifs or modulate polyQ aggregation, indicating

214 and polyQ repeat length, suggesting possible polyQ length-dependent differences in the structural pro

215 ntracellular protein aggregation, preventing polyQ peptide aggregation by chaperones should greatly i

216 As a novel approach to probing polyQ toxicity, we investigate here how some cellular an

217 Expression of aggregation-prone polyQ-containing proteins or the Amyloid-beta42 peptide,

218 mbles that found for the aggregation of pure polyQ repeats using AWSEM.

219 Previous studies have shown that pure polyQ peptides aggregate by nucleated growth polymerizat

220 by polyglutamine-expanded androgen receptor (polyQ-AR).

221 g truncated exon 1 of Htt with a 103-residue polyQ expansion that yields polyQ-Htt aggregates to inve

222 oduce the properties of a simple, 30-residue polyQ peptide (Q30) in explicit water.

223 s, are likely to be the main source of sharp polyQ length dependencies of HD.

224 mulations, negate the hypothesis of a sharp, polyQ length-dependent change in the structure of monome

225 y beta-hairpin enhancing motifs into a short polyQ sequence to generate a mutant, here called "betaHP

226 We describe here the use of very short polyQ repeat lengths in htt N-terminal fragments to slow

227 brils were essentially unchanged from simple polyQ aggregates.

228 act as potent inhibitors in trans of simple polyQ peptide aggregation.

229 A previous study of simple polyQ peptides showed that N*, the size of the critical

230 , DNAJB6, inhibits the conversion of soluble polyQ peptides into amyloid fibrils, in particular by su

231 from expansions of polyglutamine stretches (polyQ) in the huntingtin protein (Htt) that promote prot

232 of polyQ peptides far more efficiently than polyQ expanded protein fragments in vitro, we conclude t

233 proteasomal degradation in neurons and that polyQ expansion causes a partial loss of this cellular f

234 Here, we determined that polyQ-expanded ataxin-7 directly bound the Gcn5 catalyti

235 We found that polyQ-AR reduced long-term protein turnover and impaired

236 These results indicate that polyQ AR in motor neurons can produce secondary patholog

237 Our results indicate that polyQ-AR diminishes TFEB function to impair autophagy an

238 Here we report that polyQ ATXN1 oligomers can propagate locally in vivo in m

239 The polyQ expansion in AR causes it to form intracellular ag

240 The polyQ expansion increases the propensity of htt to aggre

241 The polyQ length-dependent aggregation and toxicity of these

242 The polyQ-expanded version of alpha1ACT recapitulates the pr

243 region, while at neutral pH both N17 and the polyQ become largely unstructured-thereby suggesting a m

244 stosterone (or dihydrotestosterone), and the polyQ triggers ARpolyQ misfolding and aggregation in spi

245 ndergoes sharp conformational changes as the polyQ length exceeds a threshold of 36-37 residues.

246 protein aggregation by directly binding the polyQ tract.

247 core architecture that are dominated by the polyQ stretch.

248 e generates N-ter fragments that contain the polyQ stretch and whose nuclear toxicity is well establi

249 fragments generated, that do not contain the polyQ stretch, induced toxicity via dilation of the endo

250 he mutant Htt (mHtt) proteins containing the polyQ repeat are aggregation-prone and form intracellula

251 ause proteasomes appear unable to digest the polyQ tract, which can initiate intracellular protein ag

252 re we establish how the domains flanking the polyQ tract shape the mHtt conformational landscape in v

253 In HD, the polyQ expansion in HTT alters the binding of TrkB-contai

254 difier) by mutating conserved lysines in the polyQ AR that are sites of SUMOylation.

255 e chirality of the glutamine residues in the polyQ.

256 In the second phase, beta-sheet forms in the polyQ.

257 a helical region of N17 propagates into the polyQ region, while at neutral pH both N17 and the polyQ

258 Sry protein lacking the polyQ domain was unstable, due to proteasomal degradatio

259 Alternatively, the core structure of the polyQ fibrils might also be a zipper layer with antipara

260 onal activity and reduces aggregation of the polyQ form of this protein, but it is unclear whether SU

261 partial identity to the 5' and 3'UTRs of the polyQ spinocerebellar ataxia (SCA) genes ATXN1, ATXN2, A

262 Furthermore, the assessed dimensions of the polyQ stretch of each monomer provide structural evidenc

263 ington's Disease, caused by expansion of the polyQ tract in exon 1 of the Huntingtin protein (Htt), i

264 disease caused by aberrant expansion of the polyQ tract in Huntingtin (HTT).

265 of proteins, and mutational expansion of the polyQ tract is associated with many neurodegenerative di

266 separable factors, notably the length of the polyQ tract, influence the mechanism of aggregation, its

267 The function of the polyQ tracts in many normal cytoplasmic proteins is uncl

268 vealing a dominant-negative phenotype of the polyQ-expanded ataxin-7-incorporated, catalytically inac

269 The severity of the disease depends on the polyQ repeat length, arising only in patients with prote

270 ndicate that a Leu-rich region preceding the polyQ tract causes it to become alpha-helical and appear

271 as in a murine model that recapitulates the polyQ pathology of HD (R6/2 mice).

272 Thus, our results suggest that the polyQ carrying the CT fragment of the P/Q-type channel i

273 Here we show that the polyQ domain enables wild-type ataxin 3 to interact with

274 We conclude that the polyQ domain has important roles in protein stabilizatio

275 ents involving the terminal additions to the polyQ repeats.

276 tch (N17) that is directly N-terminal to the polyQ tract in huntingtin decreases the overall solubili

277 was Htt's N17 domain sited N-terminal to the polyQ tract, which is key to enhancing aggregation and m

278 g the length of or sequences adjacent to the polyQ, altering ploidy or chaperone dosage, or deleting

279 enerate a neurotoxic conformation, while the polyQ tract alone exhibited minimal toxicity.

280 he monomers or monomer dimensions within the polyQ amyloid fibril.

281 surface-exposed hydroxyl groups that bind to polyQ peptides and may disrupt the formation of the H bo

282 cell-cycle timing control and arises due to polyQ-dependent behavior of an RNA-binding protein.

283 Gln resonances that appears to be unique to polyQ amyloid is replicated exactly in fibrils from a be

284 the HDL2 expansion may give rise to a toxic polyQ protein translated from an antisense mRNA derived

285 regation of an expanded polyglutamine tract (polyQ).

286 describe a specific function for a wild-type polyQ tract that is abrogated by a competing longer poly

287 must also be unifying mechanisms underlying polyQ toxicity.

288 rosophila expressing expanded and unexpanded polyQ HTT exon1 in the eye disc were developed.

289 cyllo-inositol lowered the number of visible polyQ-Htt aggregates and robustly decreased polyQ-Htt pr

290 observed in a Drosophila model of HD, where polyQ aggregates localize exclusively to the cytoplasm.

291 Our data support a model in which polyQ peptides containing strong beta-hairpin encouragin

292 While polyQ-expanded huntingtin (Htt) is known to accumulate i

293 o tend to be "buried" inside, explaining why polyQ domains are insoluble on their own.

294 nt production of native tag-free Httex1 with polyQ repeats ranging from 7Q to 49Q.

295 exact mechanism by which they interact with polyQ-containing, aggregation-prone proteins and interfe

296 cal findings include motor neuron loss, with polyQ-AR accumulation in intranuclear inclusions.

297 competed for by other soluble proteins with polyQ tracts in a length-dependent fashion.

298 e introduction of beta-hairpin motifs within polyQ sequences.

299 variants represent a short (CT-short without polyQs) and a long (CT-long with 27 polyQs) CT fragment.

300 th a 103-residue polyQ expansion that yields polyQ-Htt aggregates to investigate the fate of polyQ-Ht