ライフサイエンスコーパス: SCA1

1 SCA1 belongs to a growing group of neurodegenerative dis

2 SCA1 disease may be reversible by RNAi therapy, and the

3 SCA1 displays higher activity than SCA3 in the in vitro

4 SCA1 has the intriguing feature that the disease-causing

5 SCA1 is caused by the toxic effects triggered by an expa

6 SCA1 is identical to SRB9, a suppressor of a cold-sensit

7 SCA1 pathogenesis studies support a model in which the e

8 SCA1 patients lose motor coordination and develop slurre

9 SCA1(+)NGFR(+) fractions were enriched for tumor-propaga

10 so protect against spinocerebellar ataxia 1 (SCA1)-induced neurodegeneration, suggesting a general ne

11 n a mouse model of spinocerebellar ataxia 1 (SCA1).

12 which include spinocerebellar ataxia type 1 (SCA1) and Huntington disease, are progressive, untreatab

13 Spinocerebellar Ataxia type 1 (SCA1) and Huntington's disease (HD) are two polyglutamin

14 repeat causes spinocerebellar ataxia type 1 (SCA1) and several other neurodegenerative diseases.

15 physiology of spinocerebellar ataxia type 1 (SCA1) and to evaluate repeat length instability in the c

16 WT duality is spinocerebellar ataxia type 1 (SCA1) caused by an ATXN1 polyglutamine protein, although

17 carrying the spinocerebellar ataxia type 1 (SCA1) gene is modulated by subcellular distribution of a

18 carrying the spinocerebellar ataxia type 1 (SCA1) gene, a polyglutamine neurodegenerative disorder,

19 d form causes spinocerebellar ataxia type 1 (SCA1) in humans and exerts cytotoxicity in Drosophila an

20 ative disease spinocerebellar ataxia type 1 (SCA1) in the mouse, we targeted 154 CAG repeats into the

21 Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative diseas

22 Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative diseas

23 Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited progressive neurological

24 Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by abn

25 Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by exp

26 Spinocerebellar ataxia type 1 (SCA1) is a lethal neurodegenerative disorder caused by e

27 Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by an expand

28 Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the expan

29 Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the expan

30 Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the expre

31 Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder characterized by a

32 Spinocerebellar ataxia type 1 (SCA1) is a paradigmatic neurodegenerative proteinopathy,

33 ative disease Spinocerebellar ataxia type 1 (SCA1) is a polyglutamine expansion disorder characterize

34 Spinocerebellar ataxia type 1 (SCA1) is a relatively rare autosomal-dominant neurologic

35 Spinocerebellar ataxia type 1 (SCA1) is an adult-onset, dominantly inherited neurodegen

36 Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease

37 Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorde

38 Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorde

39 Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorde

40 Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorde

41 Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorde

42 Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurological disorder cau

43 Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant, polyglutamine-induced ne

44 Spinocerebellar ataxia type 1 (SCA1) is an incurable neurodegenerative disease caused b

45 Spinocerebellar ataxia type 1 (SCA1) is one of nine dominantly inherited neurodegenerat

46 Spinocerebellar ataxia type 1 (SCA1) is one of nine inherited neurodegenerative disease

47 Spinocerebellar ataxia type 1 (SCA1) is one of nine inherited, typically adult onset, p

48 Spinocerebellar ataxia type 1 (SCA1) is one of several neurodegenerative diseases cause

49 Spinocerebellar ataxia type 1 (SCA1) is one of several neurodegenerative disorders caus

50 Spinocerebellar ataxia type 1 (SCA1) is one of several neurological disorders caused by

51 Spinocerebellar ataxia type 1 (SCA1) is one such disease, characterized by loss of moto

52 Spinocerebellar ataxia type 1 (SCA1) is one such disease-caused by expansion of a polyg

53 ng pathogenic spinocerebellar ataxia type 1 (SCA1) or type 3 (SCA3) proteins in Drosophila larval den

54 n the largest spinocerebellar ataxia type 1 (SCA1) pedigree known.

55 ouse model of spinocerebellar ataxia type 1 (SCA1) suggest that neuronal dysfunction is reversible an

56 ment disorder spinocerebellar ataxia type 1 (SCA1) through a toxic gain-of-function mechanism in the

57 e toxicity in spinocerebellar ataxia type 1 (SCA1), a disease caused by a polyglutamine expansion in

58 c screens, to spinocerebellar ataxia type 1 (SCA1), a disease caused by expansion of a polyglutamine

59 sociated with spinocerebellar ataxia type 1 (SCA1), a neurodegenerative disease of late onset with va

60 ATXN1 causes spinocerebellar ataxia type 1 (SCA1), a neurodegenerative disease that impairs coordina

61 In spinocerebellar ataxia type 1 (SCA1), accumulation of polyglutamine-expanded (polyQ-exp

62 otein causing spinocerebellar ataxia type 1 (SCA1), aggregates in ubiquitin-positive nuclear inclusio

63 low levels in spinocerebellar ataxia type 1 (SCA1), and that replenishing VEGF reverses the cerebella

64 disease (HD), spinocerebellar ataxia type 1 (SCA1), dentatorubral pallidoluysian atrophy (DRPLA) Mach

65 ease (HD) and spinocerebellar ataxia type 1 (SCA1), in which the expansions are within widely express

66 ophy (DRPLA), spinocerebellar ataxia type 1 (SCA1), Machado-Joseph disease (MJD), and Friedreich atax

67 82Q] model of spinocerebellar ataxia type 1 (SCA1), we explored the hypothesis that regional differen

68 ouse model of spinocerebellar ataxia type 1 (SCA1), we identify a previously unappreciated compensato

69 mine disorder spinocerebellar ataxia type 1 (SCA1), we tested the hypothesis that cerebellar Purkinje

70 use model for spinocerebellar ataxia type 1 (SCA1), which carries an expanded CAG repeat tract at the

71 ouse model of spinocerebellar ataxia type 1 (SCA1).

72 mine disease, spinocerebellar ataxia type 1 (SCA1).

73 axin-1 causes spinocerebellar ataxia type 1 (SCA1).

74 tive disease, spinocerebellar ataxia type 1 (SCA1).

75 ion disorder, spinocerebellar ataxia type 1 (SCA1).

76 odegenerative spinocerebellar ataxia type 1 (SCA1).

77 rogression in spinocerebellar ataxia type 1 (SCA1).

78 ative disease spinocerebellar ataxia type 1 (SCA1).

79 ouse model of spinocerebellar ataxia type 1 (SCA1; B05 mice).

80 nson disease, spinocerebellar ataxia type 1 (SCA1; ref.

81 ansion causes spinocerebellar ataxia type-1 (SCA1) and triggers the formation of nuclear inclusions (

82 t form causes spinocerebellar ataxia type-1 (SCA1).

83 odel of human spinocerebellar ataxia type 1, SCA1, where mice exhibit only moderate motor impairment,

84 Forty-three controls, 55 SCA1 and 124 SCA3 carriers were included; a subset of th

85 icular, spinocerebellar ataxia type 1 and 7 (SCA1 and SCA7) patients manifest cerebellar ataxia with

86 Each of the studied 78 SCA1 patients carried an expanded allele containing a st

87 enhanced in multiple cell types in the adult SCA1 mouse cerebellum, and that activation of this signa

88 at alter proteasome distribution in affected SCA1 patient neurons.

89 co-localize in NIs both in cell culture and SCA1 postmortem neurons.

90 tive disorders such as Parkinson disease and SCA1 in humans and GAD in mice, neither ubiquitin-positi

91 um1 caused progressive motor dysfunction and SCA1-like neurodegeneration with motor impairment, prima

92 Although both HD and SCA1 are autosomal dominantly inherited, and both typica

93 Experiments in HD and SCA1 transgenic mice suggest a correlation between pheno

94 Here, we review HD and SCA1 with a focus on how their disease-specific and shar

95 including KIT(+), PDGFRalpha(+), ISL1(+)and SCA1(+)cells, side population cells, cardiospheres and e

96 ubset of polyQ disorders, including SCA3 and SCA1.

97 enable accurate distinction of wild-type and SCA1 cells.

98 units, vinculin, and spinocerebellar ataxia [SCA1]), growth factors (insulin-like growth factor bindi

99 of the most common spinocerebellar ataxias: SCA1, SCA2, SCA3, and SCA6.

100 s, Huntingtin (HTT, HD) and Ataxin 1 (ATXN1, SCA1), have unique functions and biological properties.

101 retinal degeneration), intermediate between SCA1 and SCA3/MJD, which account for 6% and 23%, respect

102 e, and a lethal CTD truncation mutation, but SCA1 deletion does not suppress alanine or glutamate sub

103 e surface phenotype of EpCAM+CD24+CD44+CD133-SCA1- and is closer in its properties to stem-like cells

104 In this study, we developed a conditional SCA1 mouse model to examine whether stopping expression

105 phenotype in a mammalian model, we crossbred SCA1 mice with mice over-expressing a molecular chaperon

106 nmt1(+/-) SCA1 mice, unlike their Dnmt1(+/+) SCA1 counterparts, closely reproduced the intergeneratio

107 Importantly, Dnmt1(+/-) SCA1 mice, unlike their Dnmt1(+/+) SCA1 counterparts, cl

108 ption is the cerebellum, which in HD, DRPLA, SCA1 and MJD has a smaller repeat relative to the other

109 human spino-cerebellar ataxia type 1 (early SCA1, 12 weeks) we find prolonged parallel fiber mGluR1-

110 s represented 5/22 (22%) and 12/38 (32%) for SCA1 and SCA3.

111 also present transmission stability data for SCA1 and FRAXA alleles spanning the thresholds and compa

112 olecular mechanisms have been implicated for SCA1, 2, 3, 7, 13, 14, 19, 22, 27 and 28, highlighting a

113 data reveal new therapeutic entry points for SCA1 and provide a proof-of-principle for tackling other

114 lar or spastic syndrome, tested positive for SCA1, SCA2, or SCA3.

115 diseases, we have created a model system for SCA1 by expressing the full-length human SCA1 gene in Dr

116 and women with positive genetic testing for SCA1, SCA2, SCA3, or SCA6 and with progressive, otherwis

117 eads toward the development of a therapy for SCA1.

118 a in serial size exclusion column fractions (SCA1, 9370 Da; SCA2, 9384 Da; SCA3, 9484 Da).

119 In acute cerebellar slices from SCA1 mice, we find that Purkinje neuron pacemaker firing

120 of this lethal phenotype and cloned a gene, SCA1 (suppressor of CTD alanine), which complements rece

121 leading to the identification of two genes (SCA1/2) mediating scAra capping.

122 After halting SCA1 expression at later stages of disease, only a parti

123 ional instability patterns observed in human SCA1 patients.

124 for SCA1 by expressing the full-length human SCA1 gene in Drosophila.

125 neurological phenotype reminiscent of human SCA1.

126 e neurological disorder that resembles human SCA1, featuring motor incoordination, cognitive deficits

127 lar ataxia (SCA) genes have been identified: SCA1, SCA2, SCA3, SCA6, and SCA7.

128 To examine whether development impacts SCA1, we used a conditional transgenic mouse model of SC

129 In SCA1 and several other polyglutamine diseases, the expan

130 In SCA1 mice, polyglutamine-expanded mutant ataxin-1 led to

131 In SCA1 mice, there was a depletion of RORalpha and a reduc

132 In SCA1, phosphorylation of ATXN1 at Ser-776 modulates dise

133 In SCA1, phosphorylation of ATXN1 at Ser776 is thought to b

134 In SCA1, the expanded polyglutamine tract is in the ataxin-

135 In SCA1, this expansion produces an abnormally long polyglu

136 02] per additional repeat unit; p=0.0128) in SCA1, short duration of follow-up (p<0.0001), lower age

137 he Arg(26) in SCA3, replacing the Gly(26) in SCA1, is predicted to cause structural changes that resu

138 he Ala(71) in SCA3, replacing the Gly(71) in SCA1, has no predictable effect on structure.

139 al spinal cord morphometric abnormalities in SCA1, SCA2, SCA3 and SCA6 using a large multisite MRI da

140 e aged; Purkinje cells, the most affected in SCA1, did not form aggregates of mutant protein until an

141 tion contributes to cognitive alterations in SCA1 remains poorly understood.

142 o the mechanisms of cognitive alterations in SCA1, we tested cognition in several mouse lines using B

143 le and decrease on female transmission as in SCA1.

144 The larger size of the hydrophobic cavity in SCA1 correlates with its higher adhesion activity.

145 ost sensitive metric to preataxic changes in SCA1 (ROC area under the curve [AUC] = 0.95), and a micr

146 ndings reinforce the central role for Cic in SCA1 cerebellar pathophysiology and suggest that only mo

147 to some improvement in motor coordination in SCA1 mice and to a modest increase in their life span.

148 eveal severe atrophy of cerebellar cortex in SCA1 patients.

149 rting the concept that cognitive deficits in SCA1 arise from a combination of cerebellar and extra-ce

150 ch might contribute to the motor deficits in SCA1, and provides new insights into the mechanisms by w

151 ells may contribute to their degeneration in SCA1 animals.

152 the selective Purkinje cell degeneration in SCA1.

153 urochemicals were significantly different in SCA1[82Q] mice at 6 weeks, before major pathological and

154 we address this by evaluating IO disease in SCA1, a prototypic inherited olivopontocerebellar atroph

155 um homeostasis sequentially downregulated in SCA1 mice.

156 characteristic of BK channel dysfunction in SCA1 mice.

157 a, are a part of the neuronal dysfunction in SCA1 transgenic mice.

158 diated increases in BK channel expression in SCA1 Purkinje neurons improves motor dysfunction and par

159 determine the pattern of gene expression in SCA1 transgenic mice at two specific times in the diseas

160 eeded to have profound therapeutic impact in SCA1.

161 ated, and leads to functional improvement in SCA1 mice even when administered at advanced stages of t

162 To elucidate cellular pathways involved in SCA1, we used DNA microarrays to determine the pattern o

163 ligomer propagation is regionally limited in SCA1 and that immunotherapy targeting extracellular olig

164 e widely expressed, the neurodegeneration in SCA1 and other polyglutamine diseases selectively involv

165 tomatic and progressive neurodegeneration in SCA1 can be noninvasively monitored using MRS.

166 Similar downregulation occurred in SCA1 human tissues.

167 A prominent site of pathology in SCA1 is cerebellar Purkinje neurons where mutant ATXN1 m

168 ng VEGF reverses the cerebellar pathology in SCA1 mice.

169 inje cells, the primary site of pathology in SCA1.

170 havioral and neuropathological phenotypes in SCA1 knock-in mice.

171 ber of non-ataxia signs reached a plateau in SCA1, SCA2, and SCA3.

172 SCA1, and tested the role of this protein in SCA1 pathology.

173 ted BG localization, which was replicated in SCA1 mouse models.

174 ata define one common pathogenic response in SCA1 and SCA7 and reveal the importance of intercellular

175 s indicate RORalpha and Tip60 have a role in SCA1 and suggest a mechanism by which compromising cereb

176 S776 of ataxin-1 also has a critical role in SCA1 pathogenesis.

177 Inhibition of HDAC3 may yet have a role in SCA1 therapy, but our study provides cautionary evidence

178 rization of these pathways and their role in SCA1 will guide research over the next several years.

179 n of the orphan nuclear receptor RORalpha in SCA1 pathogenesis.

180 ology that are very similar to those seen in SCA1 patients.

181 sponsible for the nuclear aggregates seen in SCA1, and that overexpression of a DnaJ chaperone promot

182 le some modifier genes function similarly in SCA1 and HD Drosophila models, others have model-specifi

183 underlying pathogenesis of motor symptoms in SCA1 comes from mouse models.

184 These results suggest that in SCA1 there is no clear causal relationship between the d

185 cumulates in neurons and exerts toxicity; in SCA1, this process causes progressive deterioration of m

186 n two brain regions especially vulnerable in SCA1: Although diminishing levels of both WT and mutant

187 using the genetically-precise SCA1 knock-in (SCA1-KI) mouse.

188 ng in PCs alone was not sufficient to induce SCA1-like phenotypes, while its activation in astrocytes

189 ic sequences containing pure and interrupted SCA1 and FRAXA repeats having lengths above and below th

190 rotoxicity of ataxin-1 provides insight into SCA1 pathogenesis and identifies potential targets for t

191 To investigate SCA1 pathogenesis and to gain insight into the function

192 NT5E(+) (CD73)(+) ENG(-) (CD105)(-) LY6A(+) (SCA1)(+) BMSC subpopulation.

193 Interestingly, loss of Gfi-1 mimics SCA1 phenotypes in Purkinje cells.

194 hether reducing 14-3-3 levels might mitigate SCA1 pathogenesis, we bred Sca1(154Q/+) mice to mice lac

195 logic infusion of recombinant VEGF mitigates SCA1 pathogenesis, suggesting a new therapeutic strategy

196 resent new therapeutic targets in mitigating SCA1.

197 Surprisingly, certain modifier genes modify SCA1 and HD models in opposite directions, i.e. they beh

198 enetic screens to identify genes that modify SCA1-induced neurodegeneration.

199 es the phenotype of the SCA1 knock-in mouse (SCA1(154Q/2Q)), the most physiologically relevant model

200 ataxia caused by the expression of a mutant SCA1 allele is not the result of cell death per se, but

201 and neuropathological course seen in mutant SCA1 transgenic mice.

202 Thus, expression of the mutant SCA1 allele within cerebellar Purkinje cells has diverge

203 In contrast, these mutant SCA1 mice have an increased initial exploratory behavior

204 A I patients with the three known mutations (SCA1, -2 or -3) highlights significant differences betwe

205 The ability of SCA1 and SRB mutant alleles to suppress CTD truncation m

206 therefore propose that a critical aspect of SCA1 pathogenesis involves the disruption of a nuclear m

207 n and loss of dendrites in Purkinje cells of SCA1 mice and indicate that altered somatodendritic memb

208 tic ataxin-1 inclusions in Purkinje cells of SCA1 mice.

209 After cessation of SCA1[82Q] transgene expression, mutant ataxin-1, includi

210 g a single allele of HDAC3 in the context of SCA1 was insufficient to improve cerebellar and cognitiv

211 A partial deletion of SCA1 (sca1 delta ::hisG) suppresses alanine or glutamate

212 and protein clearance in the development of SCA1.

213 s, we demonstrated that long-term feeding of SCA1-58Q mice with dantrolene alleviated age-dependent m

214 a mild exercise regimen in a mouse model of SCA1 and found a considerable improvement in survival ac

215 rexpression of CHIP in a Drosophila model of SCA1 decreases the protein steady-state levels of both e

216 ally, we find that a separate mouse model of SCA1 in which mutant ATXN1 is expressed solely in cerebe

217 Using a knock-in mouse model of SCA1 that recapitulates the selective neurodegeneration

218 used a conditional transgenic mouse model of SCA1 to delay the postnatal expression of mutant ATXN1 u

219 hosphorylation, and in a Drosophila model of SCA1, both 14-3-3 and Akt modulate neurodegeneration.

220 aused by mutant ataxin-1 in a mouse model of SCA1.

221 , the most physiologically relevant model of SCA1.

222 mine-expanded ATXN1 in a Drosophila model of SCA1.

223 or coordination deficits in a mouse model of SCA1.

224 auge disease progression in a mouse model of SCA1.

225 In inducible mouse models of SCA1 and Huntington disease, repression of mutant allele

226 genic events, we studied two mouse models of SCA1 and SCA7 that express the glutamine-expanded protei

227 In affected neurons of SCA1 patients and transgenic mice, mutant ataxin-1 accum

228 gle nuclear structure in affected neurons of SCA1 patients.

229 vidence that the selective neuropathology of SCA1 arises from modulation of a core functional activit

230 s Boat) locus, a highly conserved paralog of SCA1, and tested the role of this protein in SCA1 pathol

231 c insight into the molecular pathogenesis of SCA1 as well as other polyglutamine diseases.

232 To understand the pathogenesis of SCA1, we examined the subcellular localization of wild-t

233 llar LANP is involved in the pathogenesis of SCA1.

234 rize the developmental expression pattern of SCA1 and to identify putative functional domains in atax

235 stores the depolarized membrane potential of SCA1 Purkinje neurons by activating potassium channels,

236 These results show that the progression of SCA1 pathogenesis is dependent on the continuous express

237 tions within the (CAG)n or (CGG)n repeats of SCA1 or FRAXA, respectively, confer increased genetic st

238 The subsequent restoration of SCA1 Purkinje neuron firing correlates with the recovery

239 esent in Purkinje cells, the primary site of SCA1 cerebellar pathology.

240 ndant in Purkinje cells, the primary site of SCA1 pathogenesis; moreover, their downregulation was me

241 nd balance deficits are the core symptoms of SCA1, cognitive decline is also commonly observed in pat

242 ed in Purkinje cells, the primary targets of SCA1.

243 ell pathology is markedly worse than that of SCA1 mice.

244 urodegenerative diseases, as the toxicity of SCA1 and tau was also suppressed when PICK1 was down-reg

245 Importantly, the effect of NLK on SCA1 pathology is dependent upon NLK's enzymatic activit

246 kinje cell pathology similar to the original SCA1 mice.

247 molecular dynamics simulation, but overall, SCA1 displays a larger cavity than SCA3.

248 In particular, SCA1+ fibroblasts were enriched for numerous chemokines,

249 ntionally targeted to the secretory pathway; SCA1/2 play a role in side-chain modifications of lipoph

250 n of lineage(neg/low), CD45(pos) EpCAM(pos), SCA1(pos), CD117(neg), CD138(neg), MHCII(neg) cells as F

251 ellar atrophy, using the genetically-precise SCA1 knock-in (SCA1-KI) mouse.

252 Six SCAs, including the more prevalent SCA1, SCA2, SCA3, and SCA6 along with SCA7 and SCA17 are

253 of expanded polyglutamine (poly-Q) proteins SCA1, SCA3, and huntingtin.

254 Six genes (RGS4, SCA1, GRM4, DPYSL2, NOS1, and GRID1) met this criterion

255 ebellar pathology, as Purkinje cell specific SCA1 transgenic mice exhibit decreased anxiety-like beha

256 These findings demonstrate that SCA1 is not caused by loss of function of ataxin-1 and p

257 We found that SCA1 phenotypes could be reversed by partial suppression

258 into the function of ATXN1 and suggest that SCA1 neuropathology depends on native, not novel, protei

259 t overexpress the normal human ataxin-1 (the SCA1[30Q] line) and wild-type controls.

260 t overexpress the mutant human ataxin-1 (the SCA1[82Q] line) were measured longitudinally up to 1 yea

261 In this study we used ataxin-1, the SCA1 gene product, as a bait in the yeast two-hybrid sys

262 protein (LANP) interacts with ataxin-1, the SCA1 gene product.

263 e human ataxin-1 (the protein encoded by the SCA1 gene) and mutant ataxin-1 in the Purkinje cells of

264 Multiple neurochemicals distinguished the SCA1[82Q] mice from controls with no overlap at all ages

265 IID in the absence of a CAG expansion in the SCA1 and SCA3 genes.

266 paring the pattern of gene expression in the SCA1 ataxic B05-ataxin-1[82Q] transgenic mouse line with

267 tor cDNA, (CAG) in the HD cDNA, (CAG) in the SCA1 cDNA, (CAG) in the SCA3 cDNA and as an isolated (CA

268 tion induces a toxic gain of function in the SCA1 encoded protein ATXN1.

269 the expansion of a CAG triplet repeat in the SCA1 gene.

270 s, which, notably, were also apparent in the SCA1 individual.

271 Two prominent aspects of pathology in the SCA1 mice are the presence of cytoplasmic vacuoles and d

272 nction and Purkinje neuron morphology in the SCA1 mice.

273 and to gain insight into the function of the SCA1 gene product ataxin-1, a novel protein without homo

274 et expansion within the coding region of the SCA1 gene.

275 epleting HDAC3 improves the phenotype of the SCA1 knock-in mouse (SCA1(154Q/2Q)), the most physiologi

276 identified which are able to impinge on the SCA1 disease process.

277 The findings in this family suggest that the SCA1 gene mutation can result in a disorder similar to m

278 ocerebellar ataxia genetically linked to the SCA1 locus on chromosome 6p has been screened for the CA

279 We describe 4 members of a family with the SCA1 mutation and a dominantly inherited progressive ata

280 xpansion of a polyglutamine tract within the SCA1 gene product, ataxin-1.

281 xpansion of a polyglutamine tract within the SCA1 product, ataxin-1.

282 e expansion of a glutamine repeat within the SCA1-encoded protein ataxin-1.

283 aking advantage of the availability of three SCA1 transgenic mouse lines, each expressing a different

284 Offspring of Capicua mutant mice bred to SCA1 mice showed significant improvement of all disease

285 gions, adding another level of complexity to SCA1 pathogenesis.

286 adation of mutant ataxin-1 may contribute to SCA1 pathogenesis.

287 in complex containing RBM17, contributing to SCA1 neuropathology by means of a gain-of-function mecha

288 ontaining ATXN1 and capicua, contributing to SCA1 through a partial loss-of-function mechanism.

289 Breeding Pum1(+/-) mice to SCA1 mice (Atxn1(154Q/+)) exacerbated disease progressio

290 agate locally in vivo in mice predisposed to SCA1 following intracerebral oligomeric tissue inoculati

291 Together, SCA1, SCA2, and SCA3/MJD constitute >40% of the mutation

292 Correspondingly, in transgenic SCA1 mouse, Boat expression is greatly reduced in Purkin

293 Spinocerebellar ataxia type1 (SCA1) is one of several neurodegenerative disorders caus

294 patients, accounting for 40%, compared with SCA1 and SCA3 which account for 35% and 15%, respectivel

295 etermine the frequency of SCA2 compared with SCA1, SCA3/Machado-Joseph disease (MJD), and dentatorubr

296 cluding CCL2, CCL7, and IL-33, compared with SCA1- fibroblasts.

297 amino acid variations in SCA3, compared with SCA1.

298 A2 had higher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores.

299 increase was 2.11 (SE 0.12) in patients with SCA1, 1.49 (0.07) in patients with SCA2, 1.56 (0.08) in

300 orrelate with ataxia scores of patients with SCA1, indicating their potential as reliable biomarkers

301 early, but more slowly than in patients with SCA1, SCA2, and SCA3 (p<0.0001).

302 1, 2005, and Aug 31, 2006, 526 patients with SCA1, SCA2, SCA3, or SCA6 were enrolled.