ライフサイエンスコーパス: SCA2

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

2 rruptions that was expanded in patients with SCA2.

3 to contribute to PN dysfunction and loss in SCA2.

4 basis for altered Purkinje neuron firing in SCA2.

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

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

7 ellent candidate as a modifier of disease in SCA2.

8 e associated with premature disease onset in SCA2.

9 intranuclear inclusions are not prominent in SCA2.

10 vity is responsible for neurodegeneration in SCA2.

11 inclusions were not considered a feature in SCA2.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

26 .01] per additional SARA point; p=0.0083) in SCA2, and lower baseline SARA score (-0.03 [SE 0.01] per

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

43 Sca2 exhibits several features suggestive of its apparen

44 The SCA2 families were from different geographical and ethni

45 SCA2 foreshortens life span and is currently without sym

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

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

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

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

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

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

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

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

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

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

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

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

58 We report the genomic structure of the SCA2 gene.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

74 The cause of PC degeneration in SCA2 is unknown.

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

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

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

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

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

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

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

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

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

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

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

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

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

88 d diverse ethnic origins were observed among SCA2 kindreds.

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

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

91 pendent motor incoordination and PC death in SCA2 mice.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

106 (2+) signaling may play an important role in SCA2 pathology and also suggest that the RyanR constitut

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

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

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

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

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

112 otential therapeutic target for treatment of SCA2 patients.

113 pendent dysfunction in the firing pattern of SCA2 PCs.

114 The SCA2 phenotype is characterized by cerebellar ataxia, ne

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

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

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

118 um transients are increased and prolonged in SCA2 PNs.

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

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

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

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

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

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

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

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

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

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

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

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

131 5, and Aug 31, 2006, 526 patients with SCA1, SCA2, SCA3, or SCA6 were enrolled.

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

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

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

135 Diagnosis of SCA2 was confirmed by genetic analysis.

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

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

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

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