ライフサイエンスコーパス: SCA3

1 d ataxin 3 in spinocerebellar ataxia type 3 (SCA3).

2 inant ataxia, spinocerebellar ataxia type 3 (SCA3).

3 amine disease spinocerebellar ataxia type 3 (SCA3).

4 syndrome, tested positive for SCA1, SCA2, or SCA3.

5 can be a promising therapeutic strategy for SCA3.

6 nted 5/22 (22%) and 12/38 (32%) for SCA1 and SCA3.

7 r insight into polyglutamine diseases beyond SCA3.

8 mical trends parallel those in patients with SCA3.

9 al in early disease stages in SCA1, SCA2 and SCA3.

10 s to prepare for clinical trials in SCA1 and SCA3.

11 sly observed signs of CCAS in mouse model of SCA3.

12 ghlighting early white matter dysfunction in SCA3.

13 a signs reached a plateau in SCA1, SCA2, and SCA3.

14 represent a promising therapeutic target in SCA3.

15 overall, SCA1 displays a larger cavity than SCA3.

16 olume for the internal hydrophobic cavity in SCA3.

17 antly increased in non-converters and ataxic SCA3 (1.06+/-0.33 pg.mL-1/year, p=0.002 and 0.57+/-0.21,

18 ive functions as well as mood alterations in SCA3-84Q hemizygous transgenic mice.

19 SCA3-84Q mice also demonstrated floating behavior during

20 SCA3-84Q mice also spent more time immobile during the f

21 Moreover, SCA3-84Q mice also suffered from a decline in recognitio

22 Particularly, SCA3-84Q mice suffer from anxiety, recognition memory de

23 so noticeably improved recognition memory in SCA3-84Q mice.

24 sion, PC histology, and motor performance in SCA3-84Q mice.

25 Therefore, the SCA3-84Q mouse model may be used as a model system to te

26 Here, we demonstrated that the SCA3-84Q transgenic mice exhibited anxiety over the nove

27 umn fractions (SCA1, 9370 Da; SCA2, 9384 Da; SCA3, 9484 Da).

28 esults shed light on disease pathogenesis in SCA3, a neurodegenerative disorder caused by polyglutami

29 repeat causes spinocerebellar ataxia type-3 (SCA3), also called Machado-Joseph disease, and is cleave

30 Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an

31 Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is reported

32 Individuals with SCA1 or SCA3 and controls were enrolled from 2018-2021 in US and

33 iology of SBMA and suggest a similar role in SCA3 and Huntington's disease.

34 A key unanswered question in SCA3 and other polyglutamine diseases is the extent to w

35 ernative splicing to disease pathogenesis in SCA3 and other polyglutamine disorders.

36 for the neuroprotective effects of TUDCA in SCA3 and propose this readily available drug for clinica

37 least a subset of polyQ disorders, including SCA3 and SCA1.

38 rd morphometric abnormalities in SCA1, SCA2, SCA3 and SCA6 using a large multisite MRI dataset.

39 ses, including Huntington disease as well as SCA3 and SCA7.

40 patients with spinocerebellar ataxia type 3 (SCA3) and 5 unaffected individuals, and correctly classi

41 rophy (DRPLA) Machado-Joseph disease (MJD or SCA3) and SCA2.

42 human disease spinocerebellar ataxia type 3 (SCA3) and the yeast prion Sup35, using Drosophila as a m

43 = 28 SCA3), ataxic SCA (n = 14 SCA1, n = 37 SCA3), and control (n = 17) groups using nonparametric t

44 ents with SCA2, 1.56 (0.08) in patients with SCA3, and 0.80 (0.09) in patients with SCA6.

45 panded polyglutamine (poly-Q) proteins SCA1, SCA3, and huntingtin.

46 As, including the more prevalent SCA1, SCA2, SCA3, and SCA6 along with SCA7 and SCA17 are caused by e

47 common spinocerebellar ataxias: SCA1, SCA2, SCA3, and SCA6.

48 expands the repertoire of existing models of SCA3, and underscores the potential contribution of alte

49 The mechanisms driving neurodegeneration in SCA3 are unclear.

50 ease (HD) and spinocerebellar ataxia type 3 (SCA3) are the two most prevalent polyglutamine (polyQ) n

51 es, including spinocerebellar ataxia type 3 (SCA3), are caused by CAG repeat expansions that encode a

52 d between preataxic SCA (n = 11 SCA1, n = 28 SCA3), ataxic SCA (n = 14 SCA1, n = 37 SCA3), and contro

53 ost sensitive metric to preataxic changes in SCA3 (AUC = 0.92).

54 Spinocerebellar ataxia type 3 (SCA3) belongs to the family of polyglutamine neurodegene

55 ly and progressive feature of SCA1, SCA2 and SCA3, but not SCA6, which can be captured using quantita

56 gher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores.

57 nduction by a spinocerebellar ataxia type 3 (SCA3) C. elegans neurodegenerative disease model was sim

58 Forty-three controls, 55 SCA1 and 124 SCA3 carriers were included; a subset of the cohort (n=1

59 D cDNA, (CAG) in the SCA1 cDNA, (CAG) in the SCA3 cDNA and as an isolated (CAG) tract.

60 Analysis of a SCA3 clinical cohort showed intriguing correlations betw

61 us to determine two amino acid variations in SCA3, compared with SCA1.

62 as significantly reduced in SCA2 (d=1.6) and SCA3 (d=1.7), and the SCA2 group also showed increased e

63 tical importance of host protein function in SCA3 disease and a potential therapeutic role of ataxin-

64 Our results advance understanding of SCA3 disease mechanisms, identify additional routes for

65 ized role for oligodendrocyte dysfunction in SCA3 disease pathogenesis.

66 ic gain-of-function of mutant ATXN3 early in SCA3 disease that is transcriptionally, biochemically, a

67 e advances in spinocerebellar ataxia Type 3 (SCA3) disease understanding, much remains unknown about

68 rked reduction in mature oligodendrocytes in SCA3-disease vulnerable brain regions, and ultrastructur

69 je neurons, and at mutant ATXN3 in MSNs from SCA3 donors.

70 Our results suggest that in SCA3, early Purkinje neuron dysfunction is associated wi

71 xin-3 domains in SCA3, identify Hsc70-4 as a SCA3 enhancer, and indicate pleiotropic effects from HSP

72 ration, Purkinje neurons in a mouse model of SCA3 exhibit increased intrinsic excitability resulting

73 in exercised SCA6 models, with no benefit to SCA3 flies.

74 s in SBMA and spinocerebellar ataxia type 3 (SCA3) fly models, and monoallelic knockout of Usp7 ameli

75 s noninvasive treatment biomarkers in future SCA3 gene silencing trials.

76 e absence of a CAG expansion in the SCA1 and SCA3 genes.

77 onfirmed as elevated at the protein level in SCA3 human disease brainstem.

78 sight into the impact of ataxin-3 domains in SCA3, identify Hsc70-4 as a SCA3 enhancer, and indicate

79 xacerbated long-term degeneration induced by SCA3 in branched sensory neurons and in a well establish

80 SCA1 displays higher activity than SCA3 in the in vitro pollen tube adhesion assay.

81 ainstem, a highly vulnerable brain region in SCA3, in a series of mouse models with varying degrees o

82 SCA3 is caused by polyglutamine expansion in ataxin-3.

83 We conclude that SCA3 is not simply a disease of neurons, and the search

84 Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative diseas

85 Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by a polygl

86 -Joseph disease or spinocerebellar ataxia 3 (SCA3) is a progressive neurodegenerative disorder caused

87 Spinocerebellar ataxia type 3 (SCA3) is an adult-onset neurodegenerative disease caused

88 Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant hereditary disorder, caus

89 Spinocerebellar ataxia 3 (SCA3) is the most common autosomal dominant ataxia.

90 Spinocerebellar ataxia type 3 (SCA3) is the most common dominantly inherited ataxia, an

91 Spinocerebellar ataxia type 3 (SCA3) is the most common dominantly inherited ataxia.

92 ipulated the repeat expansion in the variant SCA3 knock-in mouse by cell-type specific Cre/LoxP recom

93 We include two SCA3 knock-in mouse models: our previously published mod

94 SCA3 knockin mice exhibit region-specific aggregate path

95 This report of a SCA3 knockin mouse expands the repertoire of existing mo

96 Spinocerebellar ataxia type 3 (SCA3)/Machado Joseph disease results from expansion of t

97 ne the frequency of SCA2 compared with SCA1, SCA3/Machado-Joseph disease (MJD), and dentatorubropalli

98 re grouped as repeat expansion SCAs, such as SCA3/Machado-Joseph disease (MJD), and rare SCAs that ar

99 solated oligodendrocyte precursor cells from SCA3 mice established that this impairment in oligodendr

100 Symptomatic SCA3 mice received intracerebroventricular treatment of

101 ASO treatment in SCA3 mice resulted in significant total choline rescue a

102 omic analysis of vulnerable brain regions in SCA3 mice to define the earliest and most robust changes

103 versed select neurochemical abnormalities in SCA3 mice, indicating the potential for these measures t

104 p with biochemical and histologic studies in SCA3 mice, we provide evidence for severe dysfunction in

105 europathology and rescue motor phenotypes in SCA3 mice.

106 e dysfunction in premanifest and symptomatic SCA3 mice.

107 the nuclei of neurons in HD mice but not in SCA3 mice.

108 earliest and most progressive dysfunction in SCA3 mice.

109 f cytoplasmic ATXN3 aggregates in neurons of SCA3 mice.

110 e cell firing and improves motor function in SCA3 mice.

111 or protein misfolding in the pathogenesis of SCA3/MJD and suggest that modulating proteasome activity

112 In neurons from SCA3/MJD brain, the proteasome localized to intranuclear

113 Together, SCA1, SCA2, and SCA3/MJD constitute >40% of the mutations leading to ADC

114 Studies of SCA3/MJD disease brain confirm these findings, showing l

115 t that an early event in the pathogenesis of SCA3/MJD may be an altered conformation of ataxin-3 with

116 licating the ubiquitin-proteasome pathway in SCA3/MJD pathogenesis.

117 EG3 and TSPOAP1 as stratification markers of SCA3/MJD progression, deserving further validation in lo

118 disease in Drosophila using a segment of the SCA3/MJD protein.

119 blood samples from an independent set of 170 SCA3/MJD subjects and 57 controls.

120 Eighty-two Dutch patients with SCA3/MJD were evaluated annually for 15 years using the

121 lar ataxia type-3 or Machado-Joseph disease (SCA3/MJD) is a member of the CAG/polyglutamine repeat di

122 Spinocerebellar ataxia type 3 (SCA3/MJD) is one of at least eight human neurodegenerati

123 bellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), an autosomal dominant ataxia caused by a poly

124 ype 3, also known as Machado-Joseph disease (SCA3/MJD), is one of at least eight inherited neurodegen

125 bellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), or an unrelated green fluorescent protein fus

126 bellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), the expanded cytosine adenine guanine (CAG) r

127 ype 3, also known as Machado-Joseph disease (SCA3/MJD), we show that the disease protein ataxin-3 acc

128 strate that ataxin-3, the disease protein in SCA3/MJD, adopts a unique conformation when expressed wi

129 degeneration), intermediate between SCA1 and SCA3/MJD, which account for 6% and 23%, respectively.

130 ribute to the rate of disease progression in SCA3/MJD.

131 ing Rad23 levels alleviates toxicity in this SCA3 model.

132 CA2 flies after chronic exercise, but not in SCA3 models, linking protein levels to exercise-based be

133 SCA3 mouse cerebellar and brainstem neurochemical trends

134 y for both motor and cognitive deficits in a SCA3 mouse model is required for the development of SCA3

135 SCA1 or SCA3 mutation carriers and controls (n = 107) underwent

136 the motor and neuropathological phenotype of SCA3 nematode and mouse models.

137 ion network analysis revealed dysfunction in SCA3 oligodendrocyte maturation.

138 generation in Spinocerebellar Ataxia Type 3 (SCA3), one of nine inherited, incurable diseases caused

139 ith positive genetic testing for SCA1, SCA2, SCA3, or SCA6 and with progressive, otherwise unexplaine

140 Aug 31, 2006, 526 patients with SCA1, SCA2, SCA3, or SCA6 were enrolled.

141 slowly than in patients with SCA1, SCA2, and SCA3 (p<0.0001).

142 Nach, an acid sensing ion channel, mitigates SCA3 pathogenesis in flies.

143 ction in oligodendrocyte maturation early in SCA3 pathogenesis.

144 d to account for non-neuronal involvement in SCA3 pathogenesis.SIGNIFICANCE STATEMENT Despite advance

145 eins that interact with Ataxin-3 to modulate SCA3 pathogenicity using Drosophila.

146 Pearson correlations were used to relate SCA3 pathology and behavior.

147 (2+) signaling may play an important role in SCA3 pathology and that Ca(2+) signaling stabilizers suc

148 new and important insights for understanding SCA3 pathology as the nucleus is likely a key site for e

149 aved in mammalian cells, transgenic mice and SCA3 patient brain tissue.

150 athogenic Atx3 accumulated in the nucleus of SCA3 patient fibroblasts following oxidative stress.

151 Moreover, recent studies have reported that SCA3 patients also exhibit symptoms of cerebellar cognit

152 However, it was recently reported that SCA3 patients also suffer from the cerebellar cognitive

153 Furthermore, brain extracts from SCA3 patients and mice show significantly lower PNKP act

154 The majority of SCA3 patients exhibit cognitive decline and approximatel

155 SCA3 patients suffer from a progressive decline in motor

156 tracts of postmortem brain tissues of HD and SCA3 patients.

157 eadily available drug for clinical trials in SCA3 patients.

158 3 cleavage might slow disease progression in SCA3 patients.

159 potential therapeutic drugs for treatment of SCA3 patients.

160 Importantly, SCA3 phenotype in Drosophila was completely amenable to

161 eraction as critical for the toxicity of the SCA3 protein, and emphasize the importance of considerin

162 ban functions downstream of toxicity of the SCA3 protein, to prevent degeneration.

163 nduced by the spinocerebellar ataxia type 3 (SCA3) protein ataxin-3, we isolated an upregulation alle

164 nduced by the spinocerebellar ataxia type 3 (SCA3) protein.

165 nocerebellar ataxia type 1 (SCA1) or type 3 (SCA3) proteins in Drosophila larval dendritic arborizati

166 iduals in the ataxic stage of SCA1, SCA2 and SCA3, relative to non-ataxic controls, had significantly

167 amine disease spinocerebellar ataxia type 3 (SCA3), remains poorly understood.

168 The Arg(26) in SCA3, replacing the Gly(26) in SCA1, is predicted to cau

169 The Ala(71) in SCA3, replacing the Gly(71) in SCA1, has no predictable

170 ease (HD) and spinocerebellar ataxia type 3 (SCA3), respectively.

171 (PNKP), is severely abrogated in both HD and SCA3 resulting in accumulation of double-strand breaks i

172 cific proteins are also responsible for SCA1-SCA3, SCA6, and SCA17; however, the converging and diver

173 SCA) genes have been identified: SCA1, SCA2, SCA3, SCA6, and SCA7.

174 iants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type, an

175 SCA3 symptoms include progressive motor decline caused b

176 Spinocerebellar ataxia Type 3 (SCA3), the most common dominantly inherited ataxia, is a

177 gh which to enhance ataxin-3 degradation for SCA3 therapy.

178 use model is required for the development of SCA3 treatment.

179 ocerebellar ataxia type 1 (SCA1) and type 3 (SCA3) using an advanced multimodal MR imaging (MRI) prot

180 s being a potential pathway mis-regulated in SCA3, we also found that down-regulation of Nach, an aci

181 In SCA3, we did not identify factors that affected progress

182 To further define pathogenic mechanisms in SCA3, we generated a mouse model in which a CAG expansio

183 To address this question in SCA3, we performed transcriptional profiling on the brai

184 , accounting for 40%, compared with SCA1 and SCA3 which account for 35% and 15%, respectively.

185 We found that feeding SCA3-YAC-84Q transgenic mice with dantrolene, a clinical