ライフサイエンスコーパス: FXTAS

1 FXTAS exhibits various movement-disorder phenotypes.

2 FXTAS is characterized by progressive development of int

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

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

5 FXTAS, and perhaps the other clinical presentations amon

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

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

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

9 Although FXTAS generally affects premutation carriers over 50 yea

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

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

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

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

14 200 repeats) include, in addition to autism, FXTAS in older males and females, and premature ovarian

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

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

17 ant was identified with probable or definite FXTAS.

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

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

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

21 there is no specific treatment available for FXTAS.

22 t early intervention might be beneficial for FXTAS patients.

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

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

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

26 cognitive or disease-modifying therapies for FXTAS.

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

28 architecture in neurons differentiated from FXTAS iPS cells.

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

30 model to study astrocyte pathology in human FXTAS.

31 fficient to cause pathology similar to human FXTAS.

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

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

34 ht to comprise the core cognitive deficit in FXTAS.

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

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

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

38 enic role in subverting neuronal function in FXTAS.

39 to parietal cortex-dependent impairments in FXTAS.

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

41 at accumulate in ubiquitinated inclusions in FXTAS patients.

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

43 have beneficial effects on verbal memory in FXTAS.

44 the likely cause of the neurodegeneration in FXTAS.

45 r basis of RNA-mediated neurodegeneration in FXTAS.

46 g mechanism of rCGG-induced neurotoxicity in FXTAS.

47 ontaining mRNA that induces neurotoxicity in FXTAS.

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

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

50 mina architecture and drives pathogenesis in FXTAS.

51 translation and contributes to pathology in FXTAS patients.

52 ulation is part of the pathogenic process in FXTAS.

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

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

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

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

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

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

59 structural impairment of the motor tracts in FXTAS.

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

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

62 ) to a predominantly intracellular location (FXTAS).

63 r neuropathological features present in male FXTAS patients.

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

65 lterations in epigenetic regulation modulate FXTAS has gone unexplored.

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

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

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

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

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

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

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

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

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

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

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

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

78 r, and parkinsonism are clinical features of FXTAS.

79 understanding of the pathologic features of FXTAS.

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

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

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

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

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

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

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

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

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

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

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

91 ays an important role in the pathogenesis of FXTAS.

92 within the FMR1 mRNA in the pathogenesis of FXTAS.

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

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

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

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

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

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

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

100 Pathologically, FXTAS is characterized by ubiquitin-positive intranuclea

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

157 n premutation astrocytes could contribute to FXTAS neuropathology.

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

159 disorders with similar movement disorders to FXTAS.

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

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

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

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

164 xicity and neurodegeneration associated with FXTAS.

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

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

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

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

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

170 e findings previously reported in males with FXTAS.

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

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

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

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

175 62.8 years), 25 premutation carriers without FXTAS (mean age = 55.4 years), and 26 normal healthy con

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

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

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

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

180 00 amplitudes were found in carriers without FXTAS.

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

182 premutation carriers, even in those without FXTAS symptoms.