ライフサイエンスコーパス: FXTAS

1 FXTAS cases showed widespread reactive gliosis in both g

2 FXTAS exhibits various movement-disorder phenotypes.

3 FXTAS is caused by a CGG-repeat expansion (CGGexp) in th

4 FXTAS is characterized by progressive development of int

5 FXTAS is thought to arise primarily from an RNA gain-of-

6 FXTAS is thought to be caused by a toxic 'gain-of-functi

7 FXTAS, and perhaps the other clinical presentations amon

8 and microscopic pathology in a series of 11 FXTAS cases (males, age 67-87 years at the time of death

9 els in the frontal cortex of 7 normal and 17 FXTAS individuals revealed that the mild FMRP decrease i

10 enome-wide profiling of cerebellar 5hmC in a FXTAS mouse model (rCGG mice) and found that rCGG mice a

11 measures showed deterioration with advancing FXTAS stage, with the strongest pattern shown in WMH vol

12 Although FXTAS generally affects premutation carriers over 50 yea

13 ed small molecule therapy is effective in an FXTAS mouse model and has the potential to treat CGGexp-

14 pic traits shared by Friedreich's ataxia and FXTAS carriers (e.g. gait ataxia, loss of coordination)

15 der male fragile X premutation carriers, and FXTAS is uncoupled from the neurodevelopmental disorder,

16 signature peptides in transfected cells, and FXTAS tissues and cells, but not in controls.

17 tabolic profiling of age-matched control and FXTAS mice cerebella at 16-20 weeks and 55 weeks.

18 ive function, tremors, below-average IQ, and FXTAS.

19 ila, cell culture, mouse disease models, and FXTAS patient brains.

20 200 repeats) include, in addition to autism, FXTAS in older males and females, and premature ovarian

21 Patients affected by FXTAS have elevated levels of ribo-rCGG repeat containin

22 Two mechanisms are proposed to cause FXTAS: RNA gain-of-function, where CGG RNA sequesters sp

23 ant was identified with probable or definite FXTAS.

24 carrier of a premutation allele will develop FXTAS, as clinical assessment fails to identify carriers

25 individual premutation carriers will develop FXTAS.

26 idth only in those individuals who developed FXTAS over time, suggests their role as potential biomar

27 The risk of developing FXTAS increases dramatically with age, with about 45% of

28 the FMR1 gene are at high risk of developing FXTAS.

29 unbiased molecular definition in diagnosing FXTAS stages while identifying potential targets for per

30 This new disorder (FXTAS) is thought to be related to elevated levels of ab

31 encing and insufficient FMR1 protein (FMRP), FXTAS is thought to be caused by 'toxicity' of expanded-

32 es as biomarkers for early diagnosis and for FXTAS disease progression, respectively.

33 there is no specific treatment available for FXTAS.

34 t early intervention might be beneficial for FXTAS patients.

35 mediated gain-of-function toxicity model for FXTAS, in which rCGG repeat-binding proteins (RBPs) coul

36 n underlying social deficits and/or risk for FXTAS.

37 hereby presenting a therapeutic strategy for FXTAS.

38 the development of targeted therapeutics for FXTAS, and more broadly as a model for the study of comm

39 cognitive or disease-modifying therapies for FXTAS.

40 of the first randomized controlled trial for FXTAS, we examined the effects of NMDA antagonist memant

41 architecture in neurons differentiated from FXTAS iPS cells.

42 We analyzed postmortem choroid plexus from FXTAS and control subjects, and found that in FXTAS iron

43 Striatal and cerebellar sections from FXTAS cases (n = 12) and controls (n = 12) were stained

44 ose misclassified usually presented a higher FXTAS stage.

45 model to study astrocyte pathology in human FXTAS.

46 fficient to cause pathology similar to human FXTAS.

47 Compounds also potently improve FXTAS-associated pre-mRNA splicing and RAN translational

48 stain nuclear and cytoplasmic aggregates in FXTAS patients and colocalize with ubiquitinated neurona

49 tive disorders, are significantly altered in FXTAS.

50 To identify key metabolic changes in FXTAS pathogenesis, we performed a genetic screen using

51 Investigating the metabolic changes in FXTAS will aid in the identification of biomarkers as we

52 Swallowing/choking problems are common in FXTAS, particularly in later stages, and may represent a

53 ht to comprise the core cognitive deficit in FXTAS.

54 hout FXTAS, and more substantial deficits in FXTAS women.

55 cent studies of mitochondrial dysfunction in FXTAS have suggested that iron dysregulation may be one

56 ble mediators of the RNA gain-of-function in FXTAS.

57 enic role in subverting neuronal function in FXTAS.

58 to parietal cortex-dependent impairments in FXTAS.

59 at accumulate in ubiquitinated inclusions in FXTAS patient brains and elicit toxicity.

60 at accumulate in ubiquitinated inclusions in FXTAS patients.

61 garding extremely elevated FMR1 increases in FXTAS and implicate glial dysregulation as a critical fa

62 Accurate FMRpolyG measurements in FXTAS patients are lacking.

63 he randomized clinical trial of memantine in FXTAS sought to use the N400 repetition effect to evalua

64 have beneficial effects on verbal memory in FXTAS.

65 r basis of RNA-mediated neurodegeneration in FXTAS.

66 the likely cause of the neurodegeneration in FXTAS.

67 g mechanism of rCGG-induced neurotoxicity in FXTAS.

68 ontaining mRNA that induces neurotoxicity in FXTAS.

69 Biochemical findings observed in FXTAS cells (lower mature frataxin, lower Complex IV and

70 eved to be the basis for the pathogenesis in FXTAS, but the exact mechanisms by which the mRNA causes

71 mina architecture and drives pathogenesis in FXTAS.

72 translation and contributes to pathology in FXTAS patients.

73 led remarkably severe astrocyte pathology in FXTAS white matter - characterized by a significant and

74 ne metabolism are significantly perturbed in FXTAS pathogenesis.

75 ulation is part of the pathogenic process in FXTAS.

76 Deficits in oxphos-more pronounced in FXTAS-affected subjects-were accompanied by a shift towa

77 n astrocytes may have an etiological role in FXTAS neuropathology.

78 ent-related brain potential (ERP) studies in FXTAS found reduced N400 repetition effect, a glutamate-

79 XTAS and control subjects, and found that in FXTAS iron accumulated in the stroma, transferrin levels

80 its are relatively mild compared to those in FXTAS males.

81 tribute to CGG repeat-associated toxicity in FXTAS and related disorders.

82 been observed to induce cellular toxicity in FXTAS, the mechanisms are unclear.

83 structural impairment of the motor tracts in FXTAS.

84 , double-blind, randomized clinical trial in FXTAS.

85 to treat CGGexp-mediated diseases, including FXTAS.

86 ain genetic and cell biological insight into FXTAS, we examined the effect of expanded CGG repeats on

87 ) to a predominantly intracellular location (FXTAS).

88 r neuropathological features present in male FXTAS patients.

89 d CGG trinucleotide repeat and used to model FXTAS, but no study has been carried out quantifying inc

90 lterations in epigenetic regulation modulate FXTAS has gone unexplored.

91 Coupled with the absence of FXTAS in fragile X syndrome patients, this suggests prem

92 the understanding of the molecular basis of FXTAS, and the emerging view of FXTAS as the end-stage o

93 g and identification of unique biomarkers of FXTAS.

94 ts in FMR1 allele as the pathogenic cause of FXTAS.

95 common neurophysiological characteristic of FXTAS patients is their inability to properly attenuate

96 potential biomarkers for early diagnosis of FXTAS.

97 pervasive physical and cognitive effects of FXTAS, no studies have examined language in symptomatic

98 ted epigenetic modulation in the etiology of FXTAS, possibly through the regulation of transcription.

99 tation carriers with no clinical evidence of FXTAS, compared with six controls.

100 The clinical expression of FXTAS occasionally resembles the phenotypes of other idi

101 Because the core feature of FXTAS is motor impairment, determining the influence of

102 viduals who do not display overt features of FXTAS (1).

103 Clinical features of FXTAS include progressive intention tremor and gait atax

104 The clinical features of FXTAS, as well as other forms of clinical involvement in

105 The clinical features of FXTAS, as well as various forms of clinical involvement

106 understanding of the pathologic features of FXTAS.

107 and exhibits the key phenotypic features of FXTAS.

108 r, and parkinsonism are clinical features of FXTAS.

109 The neuropathological hallmark of FXTAS is an intranuclear inclusion, present in both neur

110 The neuropathological hallmark of FXTAS is the presence of ubiquitin-positive intranuclear

111 The pathologic hallmark of FXTAS is the ubiquitin-positive intranuclear inclusion f

112 bodies are the neuropathological hallmark of FXTAS, which are largest and occur most frequently in as

113 r alpha is also present in the inclusions of FXTAS patient brains.

114 min A/C is present in both the inclusions of FXTAS patients and the inclusions in cell culture, sugge

115 se findings support the disease mechanism of FXTAS of rCGG repeat sequestration of specific RBPs, lea

116 eviously, we developed a Drosophila model of FXTAS and demonstrated that transcribed premutation repe

117 we utilize a transgenic Drosophila model of FXTAS that expresses a premutation-length repeat (90 CGG

118 he present study, this CGG KI mouse model of FXTAS was tested on behavioral tasks that emphasize spat

119 a genetic screen using a Drosophila model of FXTAS.

120 enetic modifiers using a Drosophila model of FXTAS.

121 at-induced toxicity in a Drosophila model of FXTAS.

122 etic screen to identify genetic modifiers of FXTAS, we demonstrate an effective method for functional

123 sed expression of PSMB5 and delayed onset of FXTAS in human FMR1 premutation carriers.

124 The pathogenesis of FXTAS is likely to involve an RNA toxic gain-of-function

125 ays an important role in the pathogenesis of FXTAS.

126 otential contribution to the pathogenesis of FXTAS.

127 within the FMR1 mRNA in the pathogenesis of FXTAS.

128 on may be a component of the pathogenesis of FXTAS; in particular, the Charcot-Marie-Tooth-type neuro

129 nly for understanding the pathophysiology of FXTAS, but also for the development of new clinical trea

130 ANN prediction of FXTAS stages was based on a combination of two imaging f

131 y diagnosis, development, and progression of FXTAS, we performed global metabolomic profiling of prem

132 is, disease prediction and, a progression of FXTAS.

133 and sex, individuals in the severe stage of FXTAS (stage 4-5) had a significantly higher risk of swa

134 had not been reported in previous studies of FXTAS, suggesting that they may be relatively protected

135 categories: those who developed symptoms of FXTAS (converters, CON) at subsequent visits and those w

136 emutation carriers who developed symptoms of FXTAS over time as compared to non-carrier healthy contr

137 at females may also manifest the symptoms of FXTAS, although more subtly and less often than their ma

138 10F), ages 58-85 years with some symptoms of FXTAS, were recruited from a larger cross-sectional stud

139 lusions from the post-mortem brain tissue of FXTAS patients.

140 as an outcome measure in clinical trials of FXTAS.

141 lar basis of FXTAS, and the emerging view of FXTAS as the end-stage of a process that begins in early

142 munohistochemistry and immunofluorescence on FXTAS patient tissues to measure their accumulation and

143 ociated with FXTAS, we took advantage of our FXTAS mouse model that expresses 90 CGG repeats in cereb

144 Pathologically, FXTAS is characterized by ubiquitin-positive intranuclea

145 n human neurons and astrocytes in postmortem FXTAS brain tissue.

146 network analyses (ANN) were used to predict FXTAS progression using data from 127 adults (noncarrier

147 and ordinal regressions were used to predict FXTAS-associated symptoms, cognitive functioning, and ex

148 Language production predicted FXTAS symptom severity, cognitive functioning, and execu

149 and (b) whether language production predicts FXTAS symptoms.

150 t data examined swallowing/choking problems, FXTAS stage, neuroimaging, and psychological distress (S

151 ative and medical disorders, and to redefine FXTAS in view of its differing presentations and associa

152 Here, we use this same FXTAS Drosophila model to conduct a chemical screen that

153 xtreme UV transient absorption spectroscopy (FXTAS) at the vanadium M2,3 edge is used to track the in

154 onia, a leading cause of death in late-stage FXTAS.

155 Fragile X-associated tremor/ataxia syndrome (FXTAS) affects motor and coordination pathways and is li

156 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a debilitating late-onset neurodegenerative di

157 Fragile X associated tremor/ataxia syndrome (FXTAS) is a late adult-onset neurodegenerative disorder

158 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late adult-onset neurodegenerative disorder

159 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affect

160 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associ

161 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused

162 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder in whi

163 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that a

164 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset progressive genetic neurodegenera

165 ile X-associated tremor and ataxia syndrome (FXTAS) is a late-onset, progressive neurodegenerative di

166 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a leading monogenic neurodegenerative disorder

167 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a multiple-system neurologic disorder caused b

168 Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a neurodegenerative disorder associated with t

169 Fragile X-associated tremor ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a CGG t

170 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a limit

171 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that affects carr

172 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that affects some

173 Fragile X associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that is the resul

174 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurological disorder that affects premutati

175 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder recog

176 Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a progressive neurodegenerative disorder that

177 Fragile X tremor/ataxia syndrome (FXTAS) is a recently described condition consisting of t

178 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently described neurodegenerative disorde

179 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently recognized neurodegenerative disord

180 Fragile X-associated tremor/ataxia syndrome (FXTAS) is a severe neurodegenerative disorder that affec

181 Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder amon

182 fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder caus

183 Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder caus

184 Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder that

185 Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder that

186 Fragile X-associated tremor/ataxia syndrome (FXTAS) is an age-related neurodegenerative disorder caus

187 fragile X-associated tremor/ataxia syndrome (FXTAS) is limited by the complex morphology of this cell

188 Fragile X-associated tremor/ataxia syndrome (FXTAS) is one such condition, resulting from a CGG trinu

189 fragile X-associated tremor/ataxia syndrome (FXTAS) pathogenesis.

190 Fragile X-associated tremor ataxia syndrome (FXTAS) results from a CGG repeat expansion in the 5' UTR

191 fragile X-associated tremor/ataxia syndrome (FXTAS) through an entirely distinct, toxic mRNA gain-of-

192 Fragile X-associated tremor/ataxia syndrome (FXTAS), a CGG repeat expansion in the 5'UTR of the fragi

193 Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative condition.

194 Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder, has bee

195 fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder manifesting cogniti

196 fragile X-associated tremor ataxia syndrome (FXTAS), ALS, and frontotemporal dementia (FTD).

197 ile X-associated tremor and ataxia syndrome (FXTAS), an RNA-mediated neurodegenerative disease has be

198 Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), Fragile X-associated Primary Ovarian Insufficien

199 fragile X-associated tremor/ataxia syndrome (FXTAS), have received additional attention during the pa

200 fragile X-associated tremor/ataxia syndrome (FXTAS), in older adult carriers.

201 fragile X-associated tremor/ataxia syndrome (FXTAS), primary ovarian insufficiency and neurodevelopme

202 fragile X-associated tremor/ataxia syndrome (FXTAS), primary ovarian insufficiency, and neurobehavior

203 including fragile X tremor ataxia syndrome (FXTAS), spinocerebellar ataxia type 8 (SCA8), SCA10, SCA

204 fragile X-associated tremor/ataxia syndrome (FXTAS), which shows very different clinical and patholog

205 fragile X-associated tremor/ataxia syndrome (FXTAS), with no targeted treatment yet established.

206 fragile X-associated tremor/ataxia syndrome (FXTAS).

207 fragile X-associated tremor/ataxia syndrome (FXTAS).

208 fragile-X-associated tremor/ataxia syndrome (FXTAS).

209 fragile-X-associated tremor/ataxia syndrome (FXTAS).

210 Fragile X-associated tremor/ataxia syndrome (FXTAS).

211 Fragile X-associated tremor/ataxia syndrome (FXTAS).

212 fragile X-associated tremor/ataxia syndrome (FXTAS).

213 fragile X-associated tremor/ataxia syndrome (FXTAS).

214 Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS).

215 y (FXPOI) and/or tremor and ataxia syndrome (FXTAS).

216 fragile X-associated tremor/ataxia syndrome (FXTAS).

217 fragile X-associated tremor/ataxia syndrome (FXTAS).

218 fragile X-associated tremor/ataxia syndrome (FXTAS).

219 fragile X-associated tremor/ataxia syndrome (FXTAS; premutation range, 55-200 repeats).

220 fragile X-associated tremor/ataxia syndrome [FXTAS]) phenotypes through an entirely distinct molecula

221 We have established that FXTAS neuropathology includes robust degeneration of ast

222 It has been proposed that FXTAS is an RNA-mediated neurodegenerative disease cause

223 n the levels of FMRP are responsible for the FXTAS pathology.

224 pecific patterns of neurodegeneration in the FXTAS brain remain incompletely characterized.

225 gical progression of other cell types in the FXTAS brain.

226 ibited weaker structural connectivity in the FXTAS group (decreased 5%-53% from controls, P </= .02).

227 In the FXTAS group, mixed-effects models demonstrated significa

228 ons in astrocytes in multiple regions of the FXTAS brain.

229 n premutation astrocytes could contribute to FXTAS neuropathology.

230 tent to which the mechanisms contributing to FXTAS also contribute to other neurodegenerative and med

231 disorders with similar movement disorders to FXTAS.

232 n size of CGG repeat length and sensitive to FXTAS disease progression across a relatively short inte

233 2) as a possible therapeutic target to treat FXTAS.

234 were recorded over the frontal lobes, where FXTAS patients showed both P300 amplitude reduction and

235 iption of movement disorders associated with FXTAS and to discuss recent observations regarding the r

236 -Marie-Tooth-type neuropathy associated with FXTAS may represent a functional laminopathy.

237 ng the metabolic alterations associated with FXTAS, especially in the brain, and the most affected re

238 fy the metabolic alterations associated with FXTAS, we took advantage of our FXTAS mouse model that e

239 xicity and neurodegeneration associated with FXTAS.

240 tion of expanded CGG repeats associated with FXTAS.

241 This study examined their association with FXTAS stages and potential as markers of disease progres

242 ants: 33 fragile X premutation carriers with FXTAS (mean age = 62.8 years), 25 premutation carriers w

243 Thirty-six male premutation carriers with FXTAS and 26 male premutation carriers without FXTAS wer

244 le and female FMR1 premutation carriers with FXTAS symptoms differ in their language use and (b) whet

245 However, fibroblasts from carriers with FXTAS symptoms presented higher FMR1 mRNA expression (3-

246 carriers without FXTAS, and 51 carriers with FXTAS; all men, ages 40 to 80 years), along with clinica

247 Unlike their male counterparts with FXTAS, none of the women had dementia.

248 erved in cortex from patients that died with FXTAS symptoms.

249 e findings previously reported in males with FXTAS.

250 ge production difficulties may co-occur with FXTAS-associated symptoms and may be a viable outcome me

251 f the FMR1 gene, including six patients with FXTAS and five premutation carriers with no clinical evi

252 as found in CNS tissue from 10 patients with FXTAS.

253 f the fragile X premutation with and without FXTAS symptomatology is warranted, as this population sh

254 d FMR1 premutation carriers with and without FXTAS) with five outcomes from brain MRI imaging and 22

255 e premutation carriers both with and without FXTAS, although these deficits are relatively mild compa

256 62.8 years), 25 premutation carriers without FXTAS (mean age = 55.4 years), and 26 normal healthy con

257 TAS and 26 male premutation carriers without FXTAS were recruited through their family relationships

258 rs (12 healthy controls, 17 carriers without FXTAS, and 51 carriers with FXTAS; all men, ages 40 to 8

259 rmance monitoring in female carriers without FXTAS, and more substantial deficits in FXTAS women.

260 of clinical involvement in carriers without FXTAS, are thought to arise from a toxic gain of functio

261 of clinical involvement in carriers without FXTAS, are thought to arise through a direct toxic gain

262 00 amplitudes were found in carriers without FXTAS.

263 However, the female carrier group without FXTAS showed more pronounced deficiencies in working mem

264 g/choking problems compared to those without FXTAS (adjusted odds ratio [aOR] = 4.17; 95%CI = 1.28-13

265 premutation carriers, even in those without FXTAS symptoms.