ライフサイエンスコーパス: SBMA

1 SBMA is caused by CAG repeat expansions in the androgen

2 SBMA is caused by CAG-polyglutamine (polyQ) repeat expan

3 SBMA is caused by expansions of a polyglutamine tract in

4 SBMA is caused by polyglutamine repeat expansions in the

5 SBMA is due to an androgen receptor containing a polyglu

6 SBMA is one of nine polyQ diseases in which polyQ expans

7 SBMA patients exhibit myopathic features, suggesting a r

8 SBMA patients with more than 70 CAGs have never been obs

9 oding for a wild-type (19 CAG repeats) and a SBMA mutant androgen receptor (52 CAG repeats) were tran

10 s a valuable reagent for the production of a SBMA mouse.

11 o permit generation of mice that will show a SBMA phenotype within their life span, we decided to obt

12 nal activity and prevents many (but not all) SBMA-associated symptoms in this mouse model.

13 SBMA symptoms, ASC-J9 treatment ameliorated SBMA symptoms by decreasing AR-97Q aggregation and incre

14 prevented toxicity and AR aggregation in an SBMA cell model and rescued primary SBMA motor neurons f

15 ate IRs were identified at the HD, SCA-7 and SBMA loci.

16 e cases, the molecular basis of many SMA and SBMA-like syndromes and most ALS cases is unknown.

17 cord and sciatic nerve of wild-type (WT) and SBMA mice at various stages of disease progression.

18 muscle-specific biomarkers useful to assess SBMA progression in mice and patients in response to pha

19 pment of spinal and bulbar muscular atrophy (SBMA or Kennedy disease).

20 ) causes spinal and bulbar muscular atrophy (SBMA) and is associated with misfolded and aggregated sp

21 Spinal and bulbar muscular atrophy (SBMA) impairs motor function in men and is linked to a C

22 Spinal and bulbar muscular atrophy (SBMA) is a heritable neurodegenerative disease caused by

23 Spinal and bulbar muscular atrophy (SBMA) is a motor neuron disease caused by polyglutamine

24 Spinal and bulbar muscular atrophy (SBMA) is a motor neuron disease caused by the expansion

25 Spinobulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by expansion

26 Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by the expan

27 Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease characterized by the lo

28 Spinal and bulbar muscular atrophy (SBMA) is a progressive neurodegenerative disease caused

29 Spinal and bulbar muscular atrophy (SBMA) is a progressive neuromuscular disease caused by p

30 Spinal bulbar muscular atrophy (SBMA) is a progressive, late onset neuromuscular disease

31 X-linked spinal and bulbar muscular atrophy (SBMA) is a rare form of motor neuron degeneration linked

32 Spinal and bulbar muscular atrophy (SBMA) is an inherited neuromuscular disorder caused by a

33 X-linked spinal and bulbar muscular atrophy (SBMA) is an inherited neuromuscular disorder characteriz

34 Spinobulbar muscular atrophy (SBMA) is an X-linked disease characterized by degenerati

35 Spinal and bulbar muscular atrophy (SBMA) is an X-linked motoneuron disease due to a CAG tri

36 X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first e

37 Spinal and bulbar muscular atrophy (SBMA) is caused by polyglutamine expansion in the androg

38 X-linked spinal and bulbar muscular atrophy (SBMA) is characterized by adult-onset muscle weakness an

39 Spinal and bulbar muscular atrophy (SBMA) is characterized by loss of motoneurons and sensor

40 Spinal and bulbar muscular atrophy (SBMA) is one of a growing number of neurodegenerative di

41 Spinal and bulbar muscular atrophy (SBMA) is one of eight inherited neurodegenerative diseas

42 esponsible for spinobulbar muscular atrophy (SBMA) that leads to selective loss of lower motor neuron

43 leads to spinal and bulbar muscular atrophy (SBMA), a neurodegenerative disease characterized by lowe

44 X-linked spinal and bulbar muscular atrophy (SBMA), a neuromuscular disorder caused by expansion of a

45 oach for spinal and bulbar muscular atrophy (SBMA), a polyglutamine disorder that affects the motor n

46 X-linked spinal and bulbar muscular atrophy (SBMA), a repeat disorder caused by polyglutamine-expande

47 Spinal and bulbar muscular atrophy (SBMA), an adult-onset neurodegenerative disease that aff

48 disease spinal and bulbar muscular atrophy (SBMA), an adult-onset, slowly progressive motor neuron d

49 ) causes spinal and bulbar muscular atrophy (SBMA), an X-linked neuromuscular disease that is fully m

50 rosis (ALS), spinal-bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA).

51 ted with spinal and bulbar muscular atrophy (SBMA), and the nuclear protein PTIP (Pax Transactivation

52 ncluding Spinal and Bulbar Muscular Atrophy (SBMA), Huntington's disease (HD), DentatoRubral and Pall

53 ncluding spinal and bulbar muscular atrophy (SBMA), Huntington's disease (HD), spinocerebellar ataxia

54 ch as X-linked spinobulbar muscular atrophy (SBMA), it is unknown whether the toxic form of the prote

55 Spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease, is a late-onset motor neuro

56 netic disorder spinobulbar muscular atrophy (SBMA).

57 dividuals with spinobulbar muscular atrophy (SBMA).

58 icity in spinal and bulbar muscular atrophy (SBMA).

59 ) causes spinal and bulbar muscular atrophy (SBMA).

60 hy (DM), spinal and bulbar muscular atrophy (SBMA, also known as Kennedy disease), Huntington disease

61 Spinal and bulbar muscular atrophy (SBMA, also known as Kennedy's disease) is one of nine ne

62 Spinal and bulbar muscular atrophy (SBMA, Kennedy's disease) is one of a group of progressiv

63 X-linked spinal and bulbar muscular atrophy (SBMA; Kennedy's disease) is a polyglutamine (polyQ) dise

64 axonal transport in motoneurons affected by SBMA.

65 uclei in the presence of its ligand to cause SBMA.

66 ne with 97 CAG expansions and characteristic SBMA-like neurogenic phenotypes.

67 , symptomatic men with genetically confirmed SBMA.

68 rid system and nor did constructs containing SBMA or DRPLA with normal or expanded polyglutamine trac

69 ncover a crucial role for NLK in controlling SBMA toxicity and reveal a novel avenue for therapy deve

70 The observed pathology of NMJs in diseased SBMA mice is likely the morphological correlates of defe

71 of polyglutamine-expanded AR is required for SBMA, we also discovered, using cell models of SBMA, tha

72 utant androgen receptor (AR) responsible for SBMA in cell, fly and mouse models.

73 mulation is a novel therapeutic strategy for SBMA.

74 tant AR was necessary but not sufficient for SBMA.

75 rowth hormone is a potential therapeutic for SBMA.

76 sible benefit from mitochondrial therapy for SBMA.

77 In SBMA the polymorphic trinucleotide CAG repeat in exon 1

78 In SBMA, the nucleus is further implicated by the critical

79 a new pathogenic pathway that is affected in SBMA and results in compromised FAT.

80 al role for muscle expression of polyQ-AR in SBMA and suggest muscle-directed therapies as effective

81 may shed light on the pathogenic cascade in SBMA and other motor neuron diseases.

82 ls, the role of motor neuron degeneration in SBMA has not been rigorously investigated.

83 ction that produces neuronal degeneration in SBMA.

84 al a novel avenue for therapy development in SBMA.

85 es evidence for mitochondrial dysfunction in SBMA cell and animal models, either through indirect eff

86 may critically mediate motor dysfunction in SBMA, but the site(s) where AR disrupts transport is unk

87 echanisms by which NLK exerts its effects in SBMA.

88 e examined the role of normal AR function in SBMA by crossing a highly representative AR YAC transgen

89 motor neurons, suggesting a role for NF-H in SBMA neuronal dysfunction.

90 , features that have both been implicated in SBMA; however, the extent to which altered AR transcript

91 e option for pharmacological intervention in SBMA and potentially other polyglutamine diseases.

92 tial targets for therapeutic intervention in SBMA.

93 ntial target for therapeutic intervention in SBMA.

94 arget tissue for therapeutic intervention in SBMA.

95 sing target for therapeutic interventions in SBMA.

96 the requirement for nuclear localization in SBMA neurotoxicity, namely the lack of mutant AR removal

97 le reactivation as a pathogenic mechanism in SBMA.

98 ests that they underlie neurodegeneration in SBMA.

99 ed by neuromuscular disease, whether NMJs in SBMA are similarly affected by disease is not known.

100 To clarify the importance of the nucleus in SBMA, we genetically manipulated the nuclear localizatio

101 uncation fragment, as such peptides occur in SBMA patients and mouse models.

102 oxidative metabolic alterations occurring in SBMA muscles and induced hypertrophy of both glycolytic

103 ubiquitin-proteasome system is preserved in SBMA models.

104 ion plays a pathogenic or protective role in SBMA.

105 ed the effect of beta-agonist stimulation in SBMA myotube cells derived from mice and patients, and i

106 etylation as powerful therapeutic targets in SBMA.

107 ide on the progression of muscle weakness in SBMA, although there were secondary indications of both

108 Although KD/SBMA has been thought of as a motor neuron disease, rece

109 y's disease/spinobulbar muscular atrophy (KD/SBMA) through poorly defined cellular mechanisms.

110 ce for disordered cellular respiration in KD/SBMA skeletal muscle.

111 order to understand factors that may modify SBMA disease progression.

112 romotes disease pathogenesis across multiple SBMA model systems.

113 We compared multiple SBMA NPC lines and documented the metabolic and autophag

114 in the sciatic nerve of adult WT and mutant SBMA mice demonstrated no overt axonal transport deficit

115 Ultrastructural analysis of SBMA mice revealed a block in autophagy pathway progress

116 ith 112 glutamines reproduce many aspects of SBMA, including slowly progressive, gender-specific moto

117 To elucidate the basis of SBMA, we expressed N-terminal truncated AR in motor neur

118 ntranuclear inclusions (NIIs), a hallmark of SBMA and the other polyglutamine diseases.

119 xamined axonal transport in a mouse model of SBMA recapitulating many aspects of the human disease.

120 e the creation of an inducible cell model of SBMA that reproduces this important characteristic of di

121 In a mouse model of SBMA, evidence for DNA damage is detected in muscle cell

122 length androgen receptor (AR) mouse model of SBMA.

123 nd a myogenic transgenic (TG) mouse model of SBMA.

124 ndent AR activation in a Drosophila model of SBMA.

125 of NMJs was examined in two mouse models of SBMA, a myogenic model that overexpresses wildtype andro

126 MA, we also discovered, using cell models of SBMA, that it is insufficient for both aggregation and t

127 neurodegeneration in cell and fly models of SBMA.

128 uscle cells) and in vivo in animal models of SBMA.

129 o play a pivotal role in the pathogenesis of SBMA using mouse models, the role of motor neuron degene

130 als a role for ligand in the pathogenesis of SBMA.

131 ay a significant role in the pathogenesis of SBMA.

132 ces both muscle and spinal cord pathology of SBMA mice.

133 therapeutic target for treating symptoms of SBMA.

134 which develop many of the motor symptoms of SBMA.

135 s to be tested in other cell types target of SBMA (i.e. muscle cells) and in vivo in animal models of

136 uperoxide dismutase-2 in affected tissues of SBMA knock-in mice.

137 Treatment of SBMA knock-in mice with clenbuterol, which was started a

138 ) and explore its therapeutic effects in our SBMA mouse model that harbors a mutant AR gene with 97 C

139 on in an SBMA cell model and rescued primary SBMA motor neurons from 5alpha-dihydrotestosterone-induc

140 FEB function to impair autophagy and promote SBMA pathogenesis.

141 al or chemical castration was used to reduce SBMA symptoms, ASC-J9 treatment ameliorated SBMA symptom

142 remarkably, loss of one copy of Nlk rescues SBMA phenotypes in mice, including extending lifespan.

143 We studied SBMA in Drosophila using an N-terminal fragment of the h

144 Our studies indicate that SBMA disease pathogenesis, both in the nervous system an

145 These findings indicate that SBMA pathogenesis is mediated by misappropriation of nat

146 Our results suggest that SBMA motor neuronopathy involves altered expression of V

147 rticularly prominent in cells expressing the SBMA androgen receptor.

148 ce of an expanded polyglutamine tract in the SBMA androgen receptor appears to enhance the production

149 n order to investigate the properties of the SBMA androgen receptor in neuronal cells, cDNAs coding f

150 reduction in transcriptional activity of the SBMA mutant as compared with wild-type androgen receptor

151 a novel therapeutic strategy to prevent the SBMA phenotype while retaining AR transcriptional functi

152 ptor translocated to the nucleus whereas the SBMA androgen receptor was mainly localized in the cytop

153 and endocrine-reproductive features of this SBMA mouse model, as AR100Tfm mice displayed accelerated

154 injection of ASC-J9 into AR-polyQ transgenic SBMA mice markedly improved disease symptoms, as seen by

155 at hormone-based therapies designed to treat SBMA patients, even with advanced disease, are likely to

156 peutic and preventative approach to treating SBMA, by disrupting the interaction between AR and AR co

157 Although the mechanisms that underlie SBMA remain unclear, defective axonal transport has been

158 , the exact pathogenic mechanisms underlying SBMA remain elusive.

159 The pathogenic mechanisms underlying SBMA remain unknown, but recent experiments show that in

160 Using SBMA AR113Q mice we analyzed proteotoxic stress-induced

161 Using SBMA as a model, we explored the relationship between pr

162 In vivo, SBMA transgenic mice overexpressing a muscle-specific is

163 y underlie motor impairments associated with SBMA.

164 tially improved motor function compared with SBMA mice.

165 ctase inhibitor dutasteride in patients with SBMA, and to identify outcome measures for use in future

166 ransgenic mice and tissue from patients with SBMA.