ライフサイエンスコーパス: glucocerebrosidase

1 d by the recessively inherited deficiency of glucocerebrosidase.

2 LIMP-2 is a specific binding partner of beta-glucocerebrosidase.

3 te-independent trafficking receptor for beta-glucocerebrosidase.

4 ive essential, lipid-processing enzyme, beta-glucocerebrosidase.

5 hydrolysis of glucosylceramide by the enzyme glucocerebrosidase.

6 ain and brainstem with therapeutic levels of glucocerebrosidase.

7 unohistochemistry demonstrated intraneuronal glucocerebrosidase.

8 lar membranes and decreased activity of beta-glucocerebrosidase.

9 on of a pH-dependent hydrolytic enzyme, beta-glucocerebrosidase.

10 pase, sphingomyelin phosphodiesterase 1, and glucocerebrosidase.

11 recessive deficiency of the lysosomal enzyme glucocerebrosidase.

12 affecting macrophages, is in the activity of glucocerebrosidase.

13 result in deficiency of the lysosomal enzyme glucocerebrosidase.

14 y decreased activity of the lysosomal enzyme glucocerebrosidase.

15 Glucocerebrosidase 1 (GBA) mutations responsible for Gau

16 Autosomal recessively inherited glucocerebrosidase 1 (GBA1) mutations cause the lysosoma

17 Mutations in glucocerebrosidase 1 (GBA1) represent the most prevalent

18 aucher disease is caused by mutations in the glucocerebrosidase 1 gene that result in deficiency of t

19 he heterozygous L444P mutation in the murine glucocerebrosidase 1 gene, and (3) transgenic mice overe

20 Both homozygous and heterozygous glucocerebrosidase 1 mutations confer an increased risk

21 Glucocerebrosidase 1 mutations, which cause Gaucher dise

22 e that 10 to 25% of Parkinson patients carry glucocerebrosidase 1 mutations.

23 Moreover, enzyme activities (glucocerebrosidase-1, glucocerebrosidase-2, hexosaminida

24 ate that ASAH1 (acid ceramidase 1) and GBA2 (glucocerebrosidase 2) enzymes that mediate glucosylsphin

25 er, enzyme activities (glucocerebrosidase-1, glucocerebrosidase-2, hexosaminidase, galactosylceramida

26 Finally, the activity of epidermal beta-glucocerebrosidase, a key lipid-processing enzyme, incre

27 -binding cassette, sub-family A, member 12), glucocerebrosidase, acid sphingomyelinase, and transglut

28 are a result of the combination of a loss of glucocerebrosidase activity and a toxic gain-of-function

29 nd neuronopathic Gaucher disease to increase glucocerebrosidase activity and decrease alpha-synuclein

30 terfering RNAs significantly attenuated acid glucocerebrosidase activity and decreased PMA-induced fo

31 stigated the effect of ambroxol treatment on glucocerebrosidase activity and on alpha-synuclein and p

32 idase chaperone, which successfully restored glucocerebrosidase activity and protein levels and reduc

33 beta-glucocerebrosidase activity and protein levels were seve

34 fully chaperoned the mutant enzyme, restored glucocerebrosidase activity and protein levels, and redu

35 Neurons show a reduction in glucocerebrosidase activity and protein levels, increase

36 These cells exhibited decreased glucocerebrosidase activity and stored the glycolipid su

37 ilable methodologies for measuring acid beta-glucocerebrosidase activity are primarily conducted in c

38 Concurrently, there was diminished beta-glucocerebrosidase activity at the stratum granulosum-st

39 ese structural series increased N370S mutant glucocerebrosidase activity by 40-90% in patient cell li

40 These data indicate that increasing glucocerebrosidase activity can influence alpha-synuclei

41 broxol treatment resulted in increased brain glucocerebrosidase activity in (1) wild-type mice, (2) t

42 The association of lower glucocerebrosidase activity in both GBA mutation carrier

43 Here, we investigated whether modulation of glucocerebrosidase activity in murine models of synuclei

44 Partial inhibition of glucocerebrosidase activity in PrP-A53T-SNCA mice using

45 tations in GBA1 also exhibit lower levels of glucocerebrosidase activity in the central nervous syste

46 ave now evaluated the efficacy of augmenting glucocerebrosidase activity in the CNS of symptomatic Gb

47 Hence, increasing glucocerebrosidase activity in the CNS represents a pote

48 Conversely, augmenting glucocerebrosidase activity in the Thy1-SNCA mouse model

49 le chaperone that has been shown to increase glucocerebrosidase activity in vitro.

50 Twenty minutes postdose, beta-glucocerebrosidase activity increased over endogenous le

51 st in vivo evidence that augmentation of CNS glucocerebrosidase activity is a potential therapeutic s

52 Acid beta-glucocerebrosidase activity is measured in molecules of

53 tion of the compounds can increase lysosomal glucocerebrosidase activity levels by therapeutically re

54 synuclein pathology, and that rescuing brain glucocerebrosidase activity might represent a therapeuti

55 A significant reduction of glucocerebrosidase activity was associated with increase

56 After the treatment, glucocerebrosidase activity was measured in the mouse br

57 Glucocerebrosidase activity was reduced in heterozygotes

58 ier recovery, attributable to decreased beta-glucocerebrosidase activity, assessed zymographically, r

59 ased lysosomal catalytic activity, decreased glucocerebrosidase activity, impaired autophagosome clea

60 By contrast, beta-glucocerebrosidase activity, which is responsible for th

61 membranes attributable to an increased beta-glucocerebrosidase activity.

62 Caveolins partially colocalize with glucocerebrosidase, an enzyme known to be critical for r

63 ector system to deliver the lysosomal enzyme glucocerebrosidase and a secreted form of GFP to the neu

64 dependent, ceramide-generating enzymes, beta-glucocerebrosidase and acidic sphingomyelinase, leading

65 tanding of the cellular relationship between glucocerebrosidase and alpha-synuclein, the potential im

66 yed as inhibitor of the human lysosomal beta-glucocerebrosidase and as pharmacological chaperone in G

67 uous, highly homologous pseudogenes for both glucocerebrosidase and metaxin at the locus increases th

68 nverse relationship exists between levels of glucocerebrosidase and oligomeric alpha-synuclein.

69 Activities of beta-glucocerebrosidase and steroid sulfatase, enzymes previo

70 activity of the lipid synthetic enzymes beta-glucocerebrosidase and steroid sulfatase, markers of bar

71 s critical to stratum corneum function, beta-glucocerebrosidase and steroid sulfatase.

72 Metaxin, a novel gene located between the glucocerebrosidase and thrombospondin 3 genes in the mou

73 usly described, in lysosomal acid lipase and glucocerebrosidase, and localizes to structures consiste

74 tions in GBA1, encoding the lysosomal enzyme glucocerebrosidase, and the synucleinopathies directly r

75 All previously described chaperones of glucocerebrosidase are enzyme inhibitors, which complica

76 tations in glycosphingolipid (GSL)-degrading glucocerebrosidase are risk factors for PD, indicating t

77 Mutations in GBA1, the gene encoding glucocerebrosidase, are associated with an enhanced risk

78 pendent lysosomal targeting, binding to beta-glucocerebrosidase (beta-GCase) and directing it to the

79 ties were attributable to a decrease in beta-glucocerebrosidase (beta-GlcCer'ase) and acidic sphingom

80 ion of the key lipid processing enzyme, beta-glucocerebrosidase (beta-GlcCer'ase), develops similar t

81 e lipids alters LIMP-2 from functioning as a glucocerebrosidase-binding monomer toward a dimeric stat

82 sly, we have shown that early treatment with glucocerebrosidase can modulate alpha-synuclein aggregat

83 Mutations in the GBA gene that encodes glucocerebrosidase cause the lysosomal storage disorder

84 ement therapy (ERT) with macrophage-targeted glucocerebrosidase (Ceredase) infusions in 5 patients (a

85 rons were treated with a novel noninhibitory glucocerebrosidase chaperone, which successfully restore

86 euticals of restricted availability, such as glucocerebrosidase, could become much cheaper and more p

87 echanism to explain this connection: loss of glucocerebrosidase creates a positive feedback loop of r

88 lucocerebrosidase gene (GBA1) gene result in glucocerebrosidase deficiency and the accumulation of it

89 au and colleagues demonstrate that lysosomal glucocerebrosidase deficiency in GD1 bone marrow MSCs is

90 D) is a lysosomal storage disorder caused by glucocerebrosidase deficiency.

91 Moreover, we find that glucocerebrosidase depletion, which has previously been

92 from the inherited deficiency of the enzyme glucocerebrosidase (EC 3.2.1.45).

93 from the deficiency of the lysosomal enzyme glucocerebrosidase (EC 3.2.1.45).

94 The lysosomal enzyme glucocerebrosidase, encoded by the glucocerebrosidase ge

95 on also led to lysosomal transport of a beta-glucocerebrosidase endoplasmic reticulum retention mutan

96 Taken together, these data suggest that glucocerebrosidase enzymatic activity could be a modifia

97 Glucocerebrosidase enzymatic activity in dried blood spo

98 We measured glucocerebrosidase enzymatic activity in dried blood spo

99 High glucocerebrosidase enzymatic activity in LRRK2 G2019S ca

100 We conclude that lower glucocerebrosidase enzymatic activity is strongly associ

101 disease were considered, they had lower mean glucocerebrosidase enzymatic activity than controls (11.

102 patients with idiopathic Parkinson's, higher glucocerebrosidase enzymatic activity was associated wit

103 mulation and ultimately resulting in reduced glucocerebrosidase enzymatic activity, lysosomal dysfunc

104 disease in GBA carriers is due to a loss of glucocerebrosidase enzymatic activity.

105 on the interaction between the reduction of glucocerebrosidase (enzymatic) activity in GBA1(+/-) car

106 A1 mutations and PD are unknown, loss of the glucocerebrosidase enzyme (GCase) activity, inhibition o

107 without GBA mutations suggests that loss of glucocerebrosidase function contributes to the pathogene

108 Although the functional gene for glucocerebrosidase (GBA) and its pseudogene (psGBA), loc

109 As mutations in the GBA gene encoding glucocerebrosidase (GBA) are known to interfere with lys

110 The inherited deficiency of the lysosomal glucocerebrosidase (GBA) due to mutations in the GBA gen

111 Gaucher disease L444P point mutation in the glucocerebrosidase (Gba) gene and exhibiting a partial e

112 Importance: Mutations in the glucocerebrosidase (GBA) gene are a risk factor for the

113 iduals with mutation in the lysosomal enzyme glucocerebrosidase (GBA) gene are at significantly high

114 utation in the LRRK2 gene, a mutation in the glucocerebrosidase (GBA) gene, or both.

115 Mutations in the glucocerebrosidase (GBA) gene, which encodes the lysosom

116 , leucine rich repeat kinase 2 (LRRK-2), and glucocerebrosidase (GBA) have shown that genetic predisp

117 D) in patients with Gaucher disease (GD) and glucocerebrosidase (GBA) heterozygotes is important for

118 motor exam score, sex, depression, and beta-glucocerebrosidase (GBA) mutation status were included i

119 Glucocerebrosidase (GBA) mutations have been associated

120 frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes G

121 disorder caused by functional deficiency of glucocerebrosidase (GBA), a lysosomal enzyme that hydrol

122 amide catalyzed by the lysosomal enzyme beta-glucocerebrosidase (GBA).

123 lysosomal glucosylceramide-degrading enzyme (glucocerebrosidase, GBA), CBE inactivated GBA2 less effi

124 While mutations in glucocerebrosidase (GBA1) are associated with an increas

125 Loss of lysosomal glucocerebrosidase (GBA1) function is responsible for se

126 Glucocerebrosidase (GBA1) gene mutations increase the ri

127 etic disease caused by mutations in the beta-glucocerebrosidase (GBA1) gene that have been also linke

128 Mutations in the acid beta-glucocerebrosidase (GBA1) gene, responsible for the lyso

129 Glucocerebrosidase (GBA1) mutations are associated with

130 GL-1 or LysoGL-1 produced by extralysosomal glucocerebrosidase GBA2 contribute to the GD1 pathophysi

131 disease, resulting from deficient lysosomal glucocerebrosidase (GC) activity, is the most common lys

132 e (GD) is characterized by loss of lysosomal glucocerebrosidase (GC) activity.

133 system, as a consequence of a deficiency in glucocerebrosidase (GC) activity.

134 n generated that delivers both a therapeutic glucocerebrosidase (GC) cDNA for the treatment of Gauche

135 They exhibited low glucocerebrosidase (GC) enzymatic activity and accumulat

136 e retroviral vector that contained the human glucocerebrosidase (GC) gene.

137 Mutations within the lysosomal enzyme beta-glucocerebrosidase (GC) result in Gaucher disease and re

138 plays a pivotal role in the delivery of beta-glucocerebrosidase (GC) to lysosomes.

139 ysosomal activity of a severely destabilized glucocerebrosidase (GC) variant associated with the deve

140 ns in the gene encoding the lysosomal enzyme glucocerebrosidase (GC).

141 lable, and although infusions of recombinant glucocerebrosidase (GCase) ameliorate the systemic effec

142 GBA encodes the lysosomal enzyme glucocerebrosidase (GCase) but the mechanisms by which l

143 (GD) results from mutations in the acid beta-glucocerebrosidase (GCase) encoding gene, GBA, which lea

144 associated with a decreased activity of the glucocerebrosidase (GCase) enzyme in brain tissues.

145 We investigated the enzymatic activity of glucocerebrosidase (GCase) in PD brains carrying heteroz

146 e, we show that functional loss of GD-linked glucocerebrosidase (GCase) in primary cultures or human

147 iciency of the lysosomal glycoside hydrolase glucocerebrosidase (GCase) leads to abnormal accumulatio

148 in the GBA1 gene that encodes lysosomal beta-glucocerebrosidase (GCase) represent an important risk f

149 Stabilization of misfolded mutant beta-glucocerebrosidase (GCase) represents an important thera

150 s have been found to be potent inhibitors of glucocerebrosidase (GCase), the beta-glucosidase enzyme

151 Mutations in glucocerebrosidase (GCase), the enzyme deficient in Gauc

152 GBA encodes for glucocerebrosidase (GCase), the enzyme deficient in the

153 e GBA gene that encodes the lysosomal enzyme glucocerebrosidase (GCase).

154 ithin the gene encoding the lysosomal enzyme glucocerebrosidase (GCase).

155 mutations in the gene coding for the enzyme glucocerebrosidase (GCase).

156 in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase).

157 BA1 gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase).

158 he glucosidase, beta, acid gene that encodes glucocerebrosidase (GCase).

159 Mutations in the glucocerebrosidase gene (GBA) are associated with Gauche

160 Carriers of mutations in the glucocerebrosidase gene (GBA) are at increased risk of d

161 thesized that specific mutations in the beta-glucocerebrosidase gene (GBA) causing neuropathic Gauche

162 Mutations in the glucocerebrosidase gene (GBA) confer a heightened risk o

163 Parkinson disease (PD) is the presence of a glucocerebrosidase gene (GBA) mutation.

164 Mutations in the glucocerebrosidase gene (GBA) represent a significant ri

165 etabolic disorder caused by mutations in the glucocerebrosidase gene (GBA), is the most common lysoso

166 Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disea

167 sease (PD) with and without mutations on the glucocerebrosidase gene (GBA).

168 pe 1 Gaucher disease (GD1), mutations in the glucocerebrosidase gene (GBA1) gene result in glucocereb

169 linical association between mutations in the glucocerebrosidase gene and the development of more prev

170 Many mutations affecting the glucocerebrosidase gene have been defined as causes of t

171 The glucocerebrosidase gene is located in a gene-rich region

172 al enzyme glucocerebrosidase, encoded by the glucocerebrosidase gene, is involved in the breakdown of

173 aucher disease is caused by mutations in the glucocerebrosidase gene, which encodes the lysosomal hyd

174 isorder caused by mutations in the acid beta-glucocerebrosidase gene.

175 storage disorder caused by mutations in the glucocerebrosidase gene.

176 lthough >100 mutations in the gene for human glucocerebrosidase have been described, most genotype-ph

177 Lysosomal acid beta-glucocerebrosidase hydrolyzes glucocerebroside to glucos

178 a small-molecule noninhibitory chaperone of glucocerebrosidase identified by high-throughput screeni

179 with alglucerase or the recombinant from of glucocerebrosidase imiglucerase is effective in treating

180 To study how glucocerebrosidase impacts parkinsonism and to evaluate

181 Importantly, hippocampal expression of glucocerebrosidase in Gba1(D409V/D409V) mice (starting a

182 an in PD, providing insight into the role of glucocerebrosidase in Lewy body disease.

183 wing infusion of recombinant human acid beta-glucocerebrosidase in mice, nonparenchymal cells are pre

184 he lysosome as measured by immunostaining of glucocerebrosidase in patient fibroblasts.

185 hanced delivery for regional distribution of glucocerebrosidase in rat and primate brains and examine

186 tions also exhibit lower enzymatic levels of glucocerebrosidase in the central nervous system (CNS),

187 Correspondingly, overexpression of glucocerebrosidase in the CNS of A53T alpha-synuclein mi

188 deno-associated virus-mediated expression of glucocerebrosidase in the CNS of symptomatic Gba1(D409V/

189 deno-associated virus-mediated expression of glucocerebrosidase in the Thy1-SNCA mouse striatum led t

190 Activity of beta-glucocerebrosidase increased after PPARalpha-activator t

191 Similar results were observed upon glucocerebrosidase inhibition by conduritol beta-epoxide

192 ate how the lipophilic moiety common to many glucocerebrosidase inhibitors might be used to optimize

193 ctural series of potent, selective, nonsugar glucocerebrosidase inhibitors.

194 l binding among the different series of beta-glucocerebrosidase inhibitors.

195 iated virus-mediated expression of exogenous glucocerebrosidase injected into the hippocampus of Gba1

196 tal-derived or recombinant form of acid beta-glucocerebrosidase is targeted to the macrophages.

197 eficient fibroblasts led to a rescue of beta-glucocerebrosidase levels and distribution.

198 icient enzymatic activity, reduced lysosomal glucocerebrosidase levels, and storage of glucosylcerami

199 t noninhibitory small-molecule chaperones of glucocerebrosidase may prove useful for the treatment of

200 tients with Gaucher disease and heterozygous glucocerebrosidase mutation carriers are at increased ri

201 ts with Gaucher disease and six heterozygous glucocerebrosidase mutation carriers with and without Pa

202 y controls, Gaucher disease and heterozygous glucocerebrosidase mutation carriers with and without Pa

203 older brother, homozygous for the same 1226G glucocerebrosidase mutation, is found on routine examina

204 In conclusion, glucocerebrosidase mutations are associated with reducti

205 Indeed, glucocerebrosidase mutations are the most frequent risk

206 cells and may provide an explanation for how glucocerebrosidase mutations increase the risk of develo

207 t need to understand the mechanisms by which glucocerebrosidase mutations predispose to neurodegenera

208 markers of oxidative stress in cells bearing glucocerebrosidase mutations.

209 human placental-derived and recombinant beta-glucocerebrosidase (pGCR and rGCR, respectively).

210 ospondin 3 (THBS3) and to the pseudogene for glucocerebrosidase (psGBA), but it transcribed in a dire

211 rmalities and kidney failure and, as an acid glucocerebrosidase receptor, impacts Gaucher and Parkins

212 o evaluate the efficacy of in vivo acid beta-glucocerebrosidase replacement therapy in animal models.

213 Mutations of GBA1, the gene encoding glucocerebrosidase, represent a common genetic risk fact

214 torage disease, is caused by a deficiency of glucocerebrosidase resulting in the impairment of glucos

215 clude a gain-of-function due to mutations in glucocerebrosidase that promotes alpha-synuclein aggrega

216 re potent, low-nanomolar inhibitors of human glucocerebrosidase that stabilize the enzyme to thermal

217 ents were monitored for antibody response to glucocerebrosidase, the active component of alglucerase.

218 beta-glucocerebrosidase, the enzyme defective in Gaucher dise

219 Mutations in GBA, the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher dise

220 They show that beta-glucocerebrosidase-the lysosomal enzyme defective in pat

221 sease involves administration of intravenous glucocerebrosidase to degrade glucocerebroside stored in

222 inergic neurons, indicating that chaperoning glucocerebrosidase to the lysosome may provide a novel t

223 cts of depleting endogenous plasma GlcCer by glucocerebrosidase treatment or of adding exogenous puri

224 Glucocerebrosidase treatment reduced plasma sensitivity

225 y to study heat-induced aggregation of human glucocerebrosidase unequivocally links loss of conformat

226 Missorting of beta-glucocerebrosidase was also evident in vivo, as protein

227 Avid and saturable uptake of modified glucocerebrosidase was found, which indicates high-affin

228 ese mice indicated that the majority of beta-glucocerebrosidase was secreted.

229 al for normal stratum corneum function, beta-glucocerebrosidase, which converts glucosylceramide to c

230 nd to be good inhibitors of recombinant beta-glucocerebrosidase with Ki values between 8.3 and 17 muM