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 e formation of intra-nuclear inclusions in a polyQ length-dependent manner during neurogenesis.

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

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

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

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

18 Signal detected for average polyQ length quantification at the protein level by our

19 Because polyQ tracts are potential therapeutic targets for these

20 lso reduces interchain entanglements between polyQ domains.

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

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

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

24 been proposed for amyloid fibrils formed by polyQ peptides.

25 anding of pathogenic mechanisms initiated by polyQ tract proteins.

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

27 tial nuclear protein trafficking pathways by polyQ-ataxin-1, a key contribution to furthering underst

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

37 aberrant expression of AR bearing different polyQ tracts and stabilized beta-catenin in prostate tum

38 monomeric Httex1 proteins of five different polyQ lengths.

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

40 ation in distinct brain regions in different polyQ diseases.

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

42 ressed polyQ proteins in vitro or endogenous polyQ proteins in Huntington's disease mouse striatum se

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

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

45 Expanded polyQ alone is not sufficient to cause inclusion formati

46 Expanded polyQ leads to htt aggregation.

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

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

49 nucleotide expansion encodes for an expanded polyQ tract in the respective proteins, resulting in tox

50 her disease-causing protein with an expanded polyQ tract(3).

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

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

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

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

55 n a specific toxic conformation for expanded polyQ.

56 nd tissues to report the effects of expanded polyQ.

57 alpha1ACT protein with a normal or expanded polyQ.

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

59 pathologic conformation of soluble expanded polyQ.

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

61 influence of sequences outside the expanded polyQ domain is revealed by finding that small modificat

62 t these compounds interact with the expanded polyQ stretch and could lower the level of mutant ataxin

63 ognize a single epitope specific to expanded polyQ.

64 Here we ask whether expanded polyQ is sufficient to cause pathology and aggregate for

65 nce full-length HTT and HTTex1 with expanded polyQ are both toxic although full-length HTT remains di

66 , in the presence of polyglutamine-expanded (polyQ-expanded) huntingtin (HTT), ADAM10 accumulates at

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

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

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

70 Ectopically expressed polyQ proteins in vitro or endogenous polyQ proteins in

71 s the question of why ubiquitously expressed polyQ proteins can cause neurodegeneration in distinct b

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

73 ile HD patients, as well as the more extreme polyQ expansions used in some HD tissue and animal model

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

75 ify such compounds with binding affinity for polyQ aggregates, we embarked on systematic structural a

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

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

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

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

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

81 g the application of ASO-based therapies for polyQ disorders in humans, offering new opportunities to

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

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

84 es from increased prominence of the globular polyQ domain.

85 caused by an expansion of a poly glutamine (polyQ) stretch in the huntingtin protein (HTT) that is n

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

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

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

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

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

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

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

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

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

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

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

97 trials that have tested ASO therapeutics in polyQ disorders.

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

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

100 ts, we investigated the effect of increasing polyQ repeat length on HTT inclusion formation, location

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

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

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

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

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

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

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

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

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

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

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

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

113 tes clearance of Huntington's disease-linked polyQ protein aggregates.

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

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

116 ring short polyQ AR versus those with longer polyQ tract AR.

117 pression of exon 1 HTT fragments with longer polyQ tracts led to the formation of intra-nuclear inclu

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

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

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

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

122 Nevertheless, given their monogenic nature, polyQ disorders are ideal candidates for therapies that

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

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

125 by enhancing the transcriptional activity of polyQ AR.

126 that influence misfolding and aggregation of polyQ disease proteins.

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

128 s overexpression promotes the aggregation of polyQ proteins and of the endogenous kinase KIN-19.

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

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

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

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

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

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

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

136 chemical restriction in seeded elongation of polyQ amyloid.

137 demonstrate here that the nuclear export of polyQ-expanded AR is impaired, even prior to the formati

138 sponsible for the impaired nuclear export of polyQ-expanded AR.

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

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

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

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

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

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

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

146 The length of polyQ tracts is inversely correlated with the risk of pr

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

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

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

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

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

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

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

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

157 observations regarding the effects of N17 on polyQ aggregation.

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

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

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

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

162 Polyglutamine (polyQ) disorders are a group of nine neurodegenerative d

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 Polyglutamine (polyQ) tract polymorphism within the human androgen rece

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

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

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

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

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

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

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

175 ELF3 contains a polyglutamine (polyQ) repeat(8-10), embedded within a predicted prion d

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

177 -expansion mutations create a polyglutamine (polyQ) tract at the N terminus of HTT that expands above

178 uromuscular disease caused by polyglutamine (polyQ) expansion in the androgen receptor (AR).

179 axias 17 (SCA17) is caused by polyglutamine (polyQ) expansion in the TATA box-binding protein (TBP).

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

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

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

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

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

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

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

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

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

189 n (mHTT) contains an expanded polyglutamine (polyQ) tract and causes Huntington's disease, an incurab

190 The expanded polyglutamine (polyQ) tract form of ataxin-1 drives disease progression

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 Abs that target the expanded polyglutamine (polyQ) tract to quantify mutant huntingtin (mHTT).

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

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

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

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

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

199 inclusions immunoreactive for polyglutamine (polyQ) antibodies.

200 Furthermore, polyglutamine (polyQ) repeats form toxic aggregates in several neurodeg

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

202 ragments with variable length polyglutamine (polyQ) tracts.

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

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

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

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

207 ying the elongated N-terminal polyglutamine (polyQ) tract misfolds and forms protein aggregates chara

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

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

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

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

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

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

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

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

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 nstream genes in tumor samples bearing short polyQ AR versus those with longer polyQ tract AR.

227 henotypes in the compound mice bearing short polyQ tract AR and stabilized beta-catenin.

228 African American men possess short polyQ tracts significantly more frequently than Caucasia

229 f Wnt/beta-catenin in combination with short polyQ AR expression in prostate tumorigenesis and sugges

230 ells from the above mouse samples with short polyQ tract AR and beta-catenin.

231 pressing stabilized beta-catenin and shorter polyQ tract AR.

232 We found that shorter polyQ length and haploinsufficiency of ATXN1 do not caus

233 Similar polyQ length-dependent effects on MSD signals were confi

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

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

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

237 have been developed in recent years for some polyQ disorders using ASO therapeutics.

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

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

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

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

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

243 es, the cellular pathways and processes that polyQ-ataxin-1 influences remain poorly understood.

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

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

246 The polyQ expansion increases the propensity of htt to aggre

247 The polyQ length-dependent aggregation and toxicity of these

248 The polyQ-expanded version of alpha1ACT recapitulates the pr

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

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

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

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

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

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

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

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

257 e chirality of the glutamine residues in the polyQ.

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

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

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

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

262 Here we find that the length of the polyQ repeat correlates with thermal responsiveness.

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

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

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

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

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

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

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 ribution of a tissue-specific protein to the polyQ protein-mediated selective neuropathology.

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

283 regation of an expanded polyglutamine tract (polyQ).

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

285 must also be unifying mechanisms underlying polyQ toxicity.

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

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

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

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

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

291 C-terminally FLAG-tagged HTT constructs with polyQ lengths representative of the general population,

292 signal detected with MW1 Ab correlated with polyQ length and doubled with a difference of only 7 glu

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

294 dation, a process that becomes impaired with polyQ expansion.

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 entially other disease-causing proteins with polyQ expansions, demonstrating the concept of lowering

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

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