ライフサイエンスコーパス: SCA2

1 ical model of spinocerebellar ataxia type 2 (SCA2).

2 N2 in transgenic mouse models of SCA type 2 (SCA2).

3 vity is responsible for neurodegeneration in SCA2.

4 inclusions were not considered a feature in SCA2.

5 LA) Machado-Joseph disease (MJD or SCA3) and SCA2.

6 rruptions that was expanded in patients with SCA2.

7 all, whereas eccentricity progressed only in SCA2.

8 to contribute to PN dysfunction and loss in SCA2.

9 basis for altered Purkinje neuron firing in SCA2.

10 in E. coli to determine the putative role of Sca2.

11 je cells (PCs) are predominantly affected in SCA2.

12 ellent candidate as a modifier of disease in SCA2.

13 e associated with premature disease onset in SCA2.

14 intranuclear inclusions are not prominent in SCA2.

15 ents with SCA1, 1.49 (0.07) in patients with SCA2, 1.56 (0.08) in patients with SCA3, and 0.80 (0.09)

16 s) and reduced PC loss observed in untreated SCA2-58Q mice by 12 months of age (quantified by stereol

17 e as well as ameliorated mood alterations in SCA2-58Q mice without affecting the firing rate of their

18 o motor, cognitive and affective symptoms in SCA2-58Q mice.

19 We previously reported that SCA2-58Q PC-specific transgenic mice exhibit anxiolytic

20 we performed a series of experiments with an SCA2-58Q transgenic mouse model that expresses human ful

21 e exclusion column fractions (SCA1, 9370 Da; SCA2, 9384 Da; SCA3, 9484 Da).

22 ouse model of spinocerebellar ataxia type 2 (SCA2), a progressive reduction in Purkinje neuron firing

23 protein cause spinocerebellar ataxia type 2 (SCA2), a rare neurodegenerative disorder.

24 ertion site of this mutant strain was within Sca2, a member of a family of large autotransporter prot

25 Sca2, a mimic of host formins [4, 5], was later shown to

26 SCA2 accounts for 13% of patients with ADCA (without ret

27 expression pattern of ataxin-2 in normal and SCA2 adult brains and cerebellum at different developmen

28 erabundant in spinocerebellar ataxia type 2 (SCA2), ALS/frontotemporal dementia patient fibroblasts,

29 use models of spinocerebellar ataxia type 2 (SCA2), an autosomal dominant polyglutamine disease.

30 mutant did not elicit fever, suggesting that Sca2 and actin-based motility are virulence factors of s

31 , and in central nervous system tissues from SCA2 and ALS animal models.

32 ffective therapeutic strategies for treating SCA2 and ALS.

33 Targeting STAU2 by RNAi normalized mTOR in SCA2 and C9ORF72 cellular models.

34 Immunizing Ifnar1(-/-);Ifngr1(-/-) mice with sca2 and ompB mutant R. parkeri protects against rechall

35 utic benefit for the patients afflicted with SCA2 and possibly other SCAs.

36 re an early and progressive feature of SCA1, SCA2 and SCA3, but not SCA6, which can be captured using

37 Individuals in the ataxic stage of SCA1, SCA2 and SCA3, relative to non-ataxic controls, had sign

38 re abnormal in early disease stages in SCA1, SCA2 and SCA3.

39 teraction of N- and C- terminal fragments of Sca2 and their contribution to actin binding and nucleat

40 the molecular mechanisms of pathogenesis of SCA2 and to identify conserved domains, we isolated and

41 taxia, motor neuron disease is often seen in SCA2, and ATXN2 CAG repeat expansions in the long normal

42 .01] per additional SARA point; p=0.0083) in SCA2, and lower baseline SARA score (-0.03 [SE 0.01] per

43 three members of this family, rOmpA (Sca0), Sca2, and rOmpB (Sca5) are involved in the interaction w

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

45 non-ataxia signs reached a plateau in SCA1, SCA2, and SCA3.

46 Together, SCA1, SCA2, and SCA3/MJD constitute >40% of the mutations lead

47 The discovery of Sca2 as an actin nucleator followed the identification o

48 nant disorder spinocerebellar ataxia type 2 (SCA2) as well as increase the risk of ALS.

49 tem, we have demonstrated that expression of Sca2 at the outer membrane of nonadherent, noninvasive E

50 SC transcriptomes were determined using an SCA2 bacterial artificial chromosome mouse model express

51 Spinocerebellar ataxia 2 (SCA2) belongs to the family of autosomal dominant cerebe

52 stem in which lineage marker (Lin)-, c-kit+, Sca2+ bone marrow cells differentiate into lytic NK1.1+

53 s; and (4) ataxin-2-like immunoreactivity in SCA2 brain tissues was more intense than in normal brain

54 ar ubiquitinated inclusions were not seen in SCA2 brain tissues.

55 In SCA2 brains, we found cytoplasmic, but not nuclear, micr

56 rkinje cells (PCs) are primarily affected in SCA2, but the cause of PC dysfunction and death in SCA2

57 ighly discordant for AO after correction for SCA2 CAG repeat length.

58 disease onset earlier than expected based on SCA2 CAG repeat size using non-parametric tests for alle

59 from patients and ataxic mice suggests that SCA2 can also share the symptoms of the cerebellar cogni

60 no extended polyglutamine tract in the mouse SCA2 cDNA, suggesting that the normal function of SCA2 i

61 SCA2 cerebellar transcriptomes were also determined, and

62 has allowed us to determine the frequency of SCA2 compared with SCA1, SCA3/Machado-Joseph disease (MJ

63 ndividuals, CSA was significantly reduced in SCA2 (d=1.6) and SCA3 (d=1.7), and the SCA2 group also s

64 that the basis for spiking abnormalities in SCA2 differ depending on disease stage, and intervention

65 However, Sca2 displays intramolecular interactions and functional

66 here that contrary to previous assumptions, Sca2 does not contain WH2 domains.

67 Sca2 exhibits several features suggestive of its apparen

68 The SCA2 families were from different geographical and ethni

69 Causative protein levels are reduced in SCA2 flies after chronic exercise, but not in SCA3 model

70 otection of speed and endurance in exercised SCA2 flies and modest protection in exercised SCA6 model

71 mobility decline and improves early death in SCA2 flies, even without exercise, coincident with disea

72 SCA2 foreshortens life span and is currently without sym

73 O in 148 individuals in 57 sibships from the SCA2 founder population in Cuba.

74 Thus, while formins are dimeric, Sca2 functions as a monomer.

75 the function of a Drosophila homolog of the SCA2 gene (Datx2).

76 An intact sca2 gene is found in the majority of pathogenic SFG ric

77 The SCA2 gene maps to chromosome 12q24 and the causative mut

78 The SCA2 gene product, ataxin-2, is a basic protein with two

79 We confirmed that the SCA2 gene product, ataxin-2, was predominantly located i

80 oding a polyglutamine tract in ataxin-2, the SCA2 gene product.

81 olyglutamine (polyQ) repeat in ataxin-2, the SCA2 gene product.

82 erent mouse tissues indicated that the mouse SCA2 gene was expressed in most tissues, but at varying

83 gion and to aid in the identification of the SCA2 gene, we have constructed a 3.9-Mb physical map, wh

84 which was used in the identification of the SCA2 gene, will be useful for the positional cloning of

85 at located in the coding region of the human SCA2 gene.

86 We report the genomic structure of the SCA2 gene.

87 d and characterized the mouse homolog of the SCA2 gene.

88 The spinocerebellar ataxia type 2 (SCA2) gene ATXN2 has a prominent role in the pathogenesi

89 The spinocerebellar ataxia type 2 (SCA2) gene has been localized to chromosome 12q24.1.

90 ed in SCA2 (d=1.6) and SCA3 (d=1.7), and the SCA2 group also showed increased eccentricity (d=1.1) re

91 Patients with SCA2 had higher CCFS scores than patients with SCA1 and

92 The gene for spinocerebellar ataxia type 2 (SCA2) has been mapped to 12q24.1.

93 For SCA2, however, there are more sequence variations yet to

94 d that both the N- and C-terminal regions of Sca2 interact with actin monomers but only weakly, where

95 Culture of lineage marker (Lin)-, c-kit+, Sca2+, interleukin (IL)-2/15Rbeta (CD122)- marrow cells

96 We conclude that SCA2 is a disease characterized by gain of function for

97 Sequence analysis revealed that SCA2 is a novel gene of unknown function.

98 SCA2 is accompanied by cerebellar degeneration and progr

99 As SCA2 is likely caused by a gain-of-toxic or gain-of-norm

100 Unlike formins, Sca2 is monomeric, but has N- and C-terminal repeat doma

101 cDNA, suggesting that the normal function of SCA2 is not dependent on this domain.

102 but the cause of PC dysfunction and death in SCA2 is poorly understood.

103 entifying function-specific therapeutics for SCA2 is problematic due to the limited knowledge of ATXN

104 we find that the actin-based motility factor Sca2 is required for dissemination from the skin to inte

105 ever, despite these functional similarities, Sca2 is structurally unrelated to eukaryotic formins and

106 Here we have shown that sca2 is transcribed and expressed in Rickettsia conorii

107 The cause of PC degeneration in SCA2 is unknown.

108 Spinocerebellar ataxia type 2 (SCA2) is a member of a group of neurodegenerative diseas

109 Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder caused by the expa

110 Spinocerebellar ataxia 2 (SCA2) is a neurodegenerative disorder characterized by p

111 Spinocerebellar ataxia type 2 (SCA2) is a polyglutamine disorder caused by a pathologic

112 Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant disorder caused by the ex

113 Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease

114 Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited disorder, whi

115 Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited, neurodegener

116 stration that spinocerebellar ataxia type 2 (SCA2) is caused by a CAG repeat expansion within the ata

117 The spinocerebellar ataxia type 2 (SCA2) is caused by a trinucleotide (CAG) expansion in th

118 Spinocerebellar ataxia type 2 (SCA2) is caused by expansion of a CAG trinucleotide repe

119 Spinocerebellar ataxia type 2 (SCA2) is caused by expansion of a polyglutamine tract in

120 Spinocerebellar ataxia type 2 (SCA2) is caused by the expansion of a polyglutamine (pol

121 d diverse ethnic origins were observed among SCA2 kindreds.

122 that in addition to other surface proteins, Sca2 may play a critical role in rickettsial pathogenesi

123 rvation among these species, we predict that Sca2 may play an important function at the rickettsial s

124 on of gene expression following treatment of SCA2 mice with an antisense oligonucleotide (ASO) loweri

125 7 have also decreased expression in SCA1 and SCA2 mice, revealing converging pathomechanisms and a co

126 of Purkinje cells in cerebellar slices from SCA2 mice, suggesting the potential therapeutic usefulne

127 7, previously identified as downregulated in SCA2 mice, targets the STAU2 3'-UTR.

128 D1 ALS mice and ALS patients with those from SCA2 mice.

129 pendent motor incoordination and PC death in SCA2 mice.

130 Sca2 mimics eukaryotic formins in that it promotes both

131 main that cooperates with other parts of the Sca2 molecule for actin binding and nucleation.

132 Like other ataxias, SCA2 most overtly affects Purkinje cells (PCs) in the ce

133 ASO7 had a similar effect in the BAC-Q72 SCA2 mouse model, and in both mouse models it normalized

134 motor, and neurophysiological phenotypes in SCA2 mouse models are normalized by lowering ATXN2 trans

135 We find in a spinocerebellar ataxia type 2 (SCA2) mouse model that calcium homeostasis in PNs is dis

136 In a guinea pig model of infection, the Sca2 mutant did not elicit fever, suggesting that Sca2 a

137 The identification of the SCA2 mutation in 31 out of 38 families with the ADCA I p

138 The SCA2 mutation is the most frequent amongst ADCA I patien

139 e also seen in an ADCA I family in which the SCA2 mutation was not identified, illustrating the impor

140 n 21q22.3 nor for spinocerebellar ataxia II (SCA2) on 12q22-q24.

141 spastic syndrome, tested positive for SCA1, SCA2, or SCA3.

142 This is the first evidence that Sca2 participates in the interaction between SFG rickett

143 ortant role of supranormal Ca2+ signaling in SCA2 pathogenesis and suggest that partial inhibition of

144 t, we investigated the mechanisms underlying SCA2 pathogenesis using cellular models.

145 endritic structure defines an early event in SCA2 pathogenesis, our findings suggest the possibility

146 atures define spinocerebellar ataxia type 2 (SCA2) pathogenesis using cultured cells, human brains an

147 (2+) signaling may play an important role in SCA2 pathology and also suggest that the RyanR constitut

148 culum plays a key role in the development of SCA2 pathology.

149 significant differences between the groups; SCA2 patients tended to have a longer disease duration,

150 um of clinical phenotypes was observed among SCA2 patients, including typical mild dominant ataxia, t

151 In SCA2 patients, the repeat was perfect and expanded to 36

152 Given the phenotypic diversity observed in SCA2 patients, we set out to determine the polymorphic n

153 otential therapeutic target for treatment of SCA2 patients.

154 pendent dysfunction in the firing pattern of SCA2 PCs.

155 The SCA2 phenotype is characterized by cerebellar ataxia, ne

156 tein, which resulted in delayed onset of the SCA2 phenotype.

157 hese results emphasize that in this model of SCA2, physiological and behavioral phenotypes precede mo

158 In SCA2 PNs, enhanced mGluR1 function is prevented by buffe

159 um transients are increased and prolonged in SCA2 PNs.

160 Pathologically, SCA2 presents as olivo-ponto-cerebellar atrophy (OPCA).

161 otransporter protein surface cell antigen 2 (Sca2) promotes actin polymerization on the surface of th

162 Furthermore, soluble Sca2 protein is capable of diminishing R. conorii invasi

163 proteins, which are nuclear, the CACNA1A and SCA2 proteins are both cytoplasmic.

164 city correlated only with ataxia severity in SCA2 (r=0.28).

165 vealed that the Rickettsia bacterial protein Sca2--recently shown to be essential for virulence and a

166 dels it normalized protein levels of several SCA2-related proteins expressed in Purkinje cells, inclu

167 f the residual variance after correction for SCA2 repeat length, we applied variance component analys

168 SCA2 results from a poly(Q) (polyglutamine) expansion in

169 Sca2's alpha-helical fold is unusual among Gram-negative

170 We show that Sca2's functional mimicry of formins is achieved through

171 ights into the underlying molecular basis of SCA2 SC phenotypes and demonstrates annotated pathways s

172 nal cord morphometric abnormalities in SCA1, SCA2, SCA3 and SCA6 using a large multisite MRI dataset.

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

174 e most common spinocerebellar ataxias: SCA1, SCA2, SCA3, and SCA6.

175 omen with positive genetic testing for SCA1, SCA2, SCA3, or SCA6 and with progressive, otherwise unex

176 5, and Aug 31, 2006, 526 patients with SCA1, SCA2, SCA3, or SCA6 were enrolled.

177 axia (SCA) genes have been identified: SCA1, SCA2, SCA3, SCA6, and SCA7.

178 Sca2 (surface cell antigen 2) is the only bacterial prot

179 hosphatase (Inpp5a) enzyme (5PP) in PCs of a SCA2 transgenic mouse model.

180 Diagnosis of SCA2 was confirmed by genetic analysis.

181 Alternative splicing seen in human SCA2 was conserved in the mouse.

182 By northern blot analysis, SCA2 was expressed during embryogenesis as early as day

183 tation: a pure CAG repeat is associated with SCA2, whereas the CAG repeat in ALS and parkinsonism is

184 The repeat occurs in the 5'-coding region of SCA2 which is a member of a novel gene family.

185 ent of Arp2/3 complex and RickA and requires Sca2, which accumulates at the bacterial pole.