ライフサイエンスコーパス: NgR

1 NgR became upregulated in RGCs following optic nerve inj

2 NgR mediates the growth-inhibiting effects of three myel

3 NgR protein expression is restricted to postnatal neuron

4 NgR(310)ecto-Fc treatment improves outcome in a rodent m

5 lt rat mixed DRG cultures, we demonstrate 1) NgR(ECD) shedding; 2) release of p75(ECD) and p75(ICD) b

6 elated (LAR) and the nogo receptors 1 and 3 (NgR), have recently been identified as receptors for the

7 function-blocking NgR ectodomain [aa 27-310; NgR(310)ecto] to spinal-injured rats.

8 lly enhanced affinity for NgR and converts a NgR antagonist peptide to an agonist.

9 T-type calcium channels as a target of Abeta-NgR signaling, mediating Abeta's inhibitory effects on c

10 MAG and Nogo-66 activate NgR independently and serve as redundant NgR ligands tha

11 he growth program of RGCs was not activated, NgR(DN) expression had no beneficial effects.

12 Live imaging studies reveal Abeta activates NgRs on the dendritic shaft of neurons, triggering an in

13 ands through either an unknown pathway after NgR- and Ca2+-dependent activation of the epidermal grow

14 Although the intrathecal application of an NgR competitive antagonist at the time of spinal cord he

15 Interactions between Lingo-1 and NgR, along with a complementary co-receptor, result in n

16 Thus, Nogo-66 and NgR have central roles in limiting axonal regeneration a

17 We conclude that Nogo-A and NgR are expressed in a mammalian-like pattern and are up

18 rved spatiotemporal regulation of Nogo-A and NgR in cell bodies and axons of RGCs during ontogeny.

19 iple sites of interaction between Nogo-A and NgR.

20 ecessary and sufficient for Nogo binding and NgR multimerization.

21 ta confirm the apposition of Nogo ligand and NgR receptor in situations of limited axonal regeneratio

22 inding of soluble fragments of Nogo, MAG and NgR to cell-surface NgR requires the entire leucine-rich

23 Both Nogo and NgR are mislocalized in AD brain samples.

24 Blocking both PirB and NgR activities leads to near-complete release from myeli

25 ents of visual system plasticity in PirB and NgR knockout mice.

26 guish the relative roles of gangliosides and NgRs in MAG-mediated inhibition of neurite outgrowth fro

27 two independent receptors, gangliosides and NgRs.

28 g of inhibitory ligands; and 3) antagonizing NgR/p75(NTR) clustering by competitive p75(ECD)/NgR inte

29 RIP of p75NTR; (iii) competitively blocking NgR/p75NTR clustering with soluble p75ECD; and (iv) cons

30 e administered the soluble function-blocking NgR ectodomain [aa 27-310; NgR(310)ecto] to spinal-injur

31 icular administration of a function-blocking NgR fragment.

32 tivation of Rho-A, cleaves the ECD from both NgR and TROY, and disinhibits neurotrophic factor (NTF)

33 d pinpoint calcium dysregulation mediated by NgRs and T-type channels as key components.

34 lure in vivo, we generated and characterized NgR-deficient mice.

35 Conversely, NgR binds to MAG-expressing cells.

36 significantly improved in the 3-day delayed NgR(310)ecto-Fc treatment group (9.5 +/- 0.7; n = 16) ve

37 /p75(NTR) clustering by competitive p75(ECD)/NgR interaction.

38 In DRGNs, dMAG inhibition was exclusively NgR-dependent, whereas in CGNs it was exclusively gangli

39 Introduction of exogenous NgR confers OMgp responsiveness to otherwise insensitive

40 uman embryonic kidney (HEK) cells expressing NgR, p75(NTR) was required for MAG-induced intracellular

41 and with substantially enhanced affinity for NgR and converts a NgR antagonist peptide to an agonist.

42 s have identified a potential coreceptor for NgR as p75(NTR), and a second-messenger pathway involvin

43 ery demonstrates a therapeutic potential for NgR antagonism in traumatic spinal cord injury.

44 ith the function of p75 as a co-receptor for NgR.

45 p75 is required for NgR-mediated signalling, as neurons from p75 knockout mi

46 ults thus fail to support a central role for NgR in axonal growth inhibition in vitro or in corticosp

47 inhibit regeneration, precipitates NgR from NgR-expressing cells, DRG, and cerebellar neurons.

48 However, neurite outgrowth from NgR-deficient postnatal dorsal root ganglion or cerebell

49 Taken together, our studies identify NgRs as a family of receptors (or components of receptor

50 New findings implicate NgR as a point of convergence in signal transduction for

51 in secreted APPalpha and Abeta, implicating NgR as a blocker of secretase processing of APP.

52 Importantly, NgR antibody, soluble NgR, or dominant-negative NgR each

53 In NgR-/- mice, plasticity during the critical period is no

54 s and Ca2+ elevation, both in neurons and in NgR/p75(NTR)-expressing HEK cells.

55 Changes in NgR level produce parallel changes in secreted APPalpha

56 g of corticospinal and raphespinal fibers in NgR(310)ecto-Fc-treated animals correlates with improved

57 Nogo transcripts are up-regulated in NgR mutants, indicating that NgR regulates Nogo in vivo.

58 -terminal base of the LRR may play a role in NgR association with the p75 coreceptor.

59 To investigate NgR specificity and multi-ligand binding, we determined

60 esponsive to myelin and to each of the known NgR ligands.

61 Mice lacking NgR are viable but display hypoactivity and motor impair

62 Mutant mice lacking NgR or Nogo-AB recover complex motor function after stro

63 nal fibers do not regenerate in mice lacking NgR, regeneration of some raphespinal and rubrospinal fi

64 DRG neurons lacking NgR do not bind Nogo-66, and their growth cones are not

65 bitory signalling by (i) antagonizing ligand/NgR binding with metalloproteinase-cleaved Nogo-A peptid

66 neuronal activity, a response that may limit NgR function and facilitate activity-dependent synapse d

67 1 is the founding member of the three-member NgR family, whereas Nogo-A (RTN4A) belongs to a four-mem

68 7 chick retinal ganglion cells with mutated NgR demonstrates that the NgR C-terminal domain is requi

69 antibody, soluble NgR, or dominant-negative NgR each prevent inhibition of neurite outgrowth by MAG.

70 MAG-induced collapse, and dominant-negative NgR eliminates MAG inhibition of neurite outgrowth.

71 Neither NgR-nor p75(NTR)-deficient mice showed enhanced regenera

72 expressing a dominant-negative form of NgR (NgR(DN)) increased axon regeneration several-fold; howev

73 The receptor for Nogo (NgR) has been identified as an axonal glycosyl-phosphati

74 While a GPI-linked receptor for Nogo (NgR) has been identified, MAG's receptor is unknown.

75 e whether blockade of the Nogo-NogoReceptor (NgR) pathway might enhance axonal sprouting and thereby

76 However, the absence of NgR has no effect on inhibition of neurite outgrowth in

77 Here, we identify competitive antagonists of NgR derived from amino-terminal peptide fragments of Nog

78 immunoprecipitation showed an association of NgR with p75(NTR) that can be disrupted by an antibody a

79 Thus, the peripheral association of NgR(310)ecto-Fc with central Abeta residues provides an

80 ll-derived factor/NTF-induced attenuation of NgR/p75NTR signalling suppresses EGFR activation, thereb

81 Transgenic or viral blockade of NgR function allows axonal sprouting in vivo.

82 Administration of exogenous blockers of NgR or NgR ligands promotes the regeneration of descendi

83 wann cell-derived factor-induced cleavage of NgR and Nogo-A, and inactivation of p75NTR signalling by

84 Cleavage of NgR and other GPI-linked proteins from the cell surface

85 Thus, TACE-induced cleavage of NgR and RIP of p75(NTR) abrogates axon growth inhibitory

86 ructure analysis, as well as a comparison of NgR surface residues not conserved in NgR2 and NgR3, ide

87 To assess the contribution of NgR to mediating myelin inhibitory signals and regenerat

88 However, genetic deletion of NgR has only a modest disinhibitory effect, suggesting t

89 blastoma culture, and targeted disruption of NgR expression increases transgenic mouse brain Abeta le

90 active ligand-binding soluble ectodomain of NgR.

91 The beneficial behavioral effects of NgR(310)ecto-Fc correlated with sprouting of raphespinal

92 are rendered MAG-sensitive by expression of NgR.

93 ruses expressing a dominant-negative form of NgR (NgR(DN)) increased axon regeneration several-fold;

94 Here we analyze the function of NgR domains in outgrowth inhibition.

95 neration in the CNS and that inactivation of NgR functioning greatly enhances axon regeneration provi

96 ligand-binding domain can act independent of NgR.

97 chors, or by NEP1-40, a peptide inhibitor of NgR.

98 hosphatidylinositol (GPI)-anchored nature of NgR indicates the requirement for additional transmembra

99 To explore the necessity of NgR for responses to myelin inhibitors and for restricti

100 Overexpression of NgR decreases Abeta production in neuroblastoma culture,

101 The percentage of NgR(310)ecto-Fc-treated animals able to support their we

102 e conclude that p75(NTR) is a co-receptor of NgR for MAG signaling and a potential therapeutic target

103 phin receptor (p75(NTR)) is a co-receptor of NgR for MAG signaling.

104 e entire leucine-rich repeat (LRR) region of NgR, but not other portions of the protein.

105 results demonstrate that down-regulation of NgR expression is a potential approach for inhibiting am

106 at assessing the physiological relevance of NgR-mediated protein-protein interactions to axon regene

107 Here, we consider the potential role of NgR mechanisms in AD.

108 at concave side of the solenoid structure of NgR.

109 Interfering with the OMgp/NgR pathway may allow lesioned axons to regenerate after

110 Soluble NgR(OMNI) (NgR(OMNI)-Fc) binds strongly to membrane-bound inhibitor

111 firm conclusion about the role of Nogo-66 or NgR.

112 ministration of exogenous blockers of NgR or NgR ligands promotes the regeneration of descending axon

113 and MAG, and their common receptor NgR1 (or NgR).

114 e identified, do not bind Nogo, MAG, OMgp or NgR.

115 Blocking the p75-NgR interaction also reduces the activities of these inh

116 The benefits of peripheral NgR administration are evident when therapy is initiated

117 potential therapeutic benefit of peripheral NgR-mediated Abeta clearance in APPswe/PSEN-1deltaE9 tra

118 ration is also present after pharmacological NgR blockade, but not in ngr1(-/-) mice.

119 Thus, physiological NgR signaling from myelin-derived Nogo, MAG, and OMgp co

120 does not inhibit regeneration, precipitates NgR from NgR-expressing cells, DRG, and cerebellar neuro

121 Purified NgR(310)ecto-Fc protein was delivered intrathecally afte

122 The soluble Nogo-66 receptor (NgR(310)ecto-Fc) protein, which can neutralize three mye

123 find that mutations in the Nogo-66 receptor (NgR) affect cessation of ocular dominance plasticity.

124 ein, all bind to an axonal Nogo-66 receptor (NgR) and at least partially account for this lack of CNS

125 glycoprotein), bind to the Nogo-66 receptor (NgR) and inhibit axonal growth in vitro.

126 ting of the ligand-binding Nogo-66 receptor (NgR) and two transmembrane coreceptors, p75 and LINGO-1.

127 viously, we found that the Nogo-66 receptor (NgR) interacts physically with both Abeta and the amyloi

128 igodendrocyte surface with Nogo-66 Receptor (NgR) on axons has been suggested to play an important ro

129 A Nogo to Nogo-66 receptor (NgR) pathway contributes to determining the ability of a

130 f these proteins bind to a Nogo-66 receptor (NgR) to inhibit axonal outgrowth in vitro.

131 domains of Nogo binds to a Nogo-66 receptor (NgR) to inhibit axonal outgrowth.

132 th inhibitory ligands, the Nogo-66 receptor (NgR), complexes with LINGO-1 and either the low-affinity

133 nchored subunit termed the Nogo-66 receptor (NgR).

134 brane protein Nogo and the Nogo-66 receptor (NgR).

135 utgrowth through an axonal Nogo-66 receptor (NgR).

136 with high affinity to the Nogo-66 receptor (NgR).

137 Nogo-A is mediated by the Nogo-66 receptor (NgR).

138 ns that bind to a neuronal Nogo-66 receptor (NgR/NgR1) to limit axonal regeneration after central ner

139 nism of Nogo signaling through its receptor (NgR) is critical to developing strategies for overcoming

140 ng a targeted deletion of the Nogo receptor (NgR(-/-)) unmasked a strong plasticity of preference con

141 on library and identified the Nogo receptor (NgR) as a high-affinity OMgp-binding protein.

142 Neuronal Nogo receptor (NgR) binds to each of the three inhibitors and has been

143 ired as a co-receptor for the Nogo receptor (NgR) to mediate the activity of myelin-associated inhibi

144 an axon surface protein, the Nogo receptor (NgR), may play a role in this process through an unprece

145 When associated with the Nogo receptor (NgR), the transmembrane receptor p75NTR signals growth c

146 Nogo receptor (NgR)-mediated control of axon growth relies on the centr

147 ppressing the activity of the Nogo receptor (NgR).

148 heir effects through the same Nogo receptor (NgR).

149 phosphatidylinositol-anchored Nogo receptor (NgR).

150 ion of several members of the Nogo receptor (NgR)/RhoA pathway improved the capacity of injured axons

151 of these factors bind to the Nogo receptor, NgR, which is expressed on axons.

152 ructurally, interact with the same receptor, NgR.

153 hosphatidylinositol-anchored Nogo receptors (NgRs) as exclusive axonal receptors for MAG.

154 ate NgR independently and serve as redundant NgR ligands that may limit axonal regeneration after CNS

155 After pathological trauma, similar NgR signaling limits functional recovery and axonal rege

156 Soluble NgR(OMNI) (NgR(OMNI)-Fc) binds strongly to membrane-boun

157 Infusion of a soluble NgR fragment reduces Abeta levels, amyloid plaque deposi

158 Importantly, NgR antibody, soluble NgR, or dominant-negative NgR each prevent inhibition of

159 The ability of soluble NgR(310)ecto to promote axon growth and locomotor recove

160 inhibitory signaling; 2) shedding of soluble NgR(ECD), which acts as a competitive antagonist to NgR

161 In transgenic mice, subcutaneous NgR(310)ecto-Fc treatment reduces brain Abeta plaque loa

162 agments of Nogo, MAG and NgR to cell-surface NgR requires the entire leucine-rich repeat (LRR) region

163 xonal outgrowth in vitro, demonstrating that NgR mediates a significant portion of axonal outgrowth i

164 up-regulated in NgR mutants, indicating that NgR regulates Nogo in vivo.

165 These data suggest that NgR mediates a significant fraction of myelin inhibition

166 The NgR family is downregulated by neuronal activity, a resp

167 The NgR glycosylphosphatidylinositol domain is not essential

168 The NgR ligand-binding domain promotes neurite outgrowth on

169 The NgR protein is detected selectively in neurons and is pr

170 The NgR provides a novel site for modifying the course of AD

171 The NgR structure analysis, as well as a comparison of NgR s

172 fold to simultaneously bind and assemble the NgR complex components during activation on a membrane.

173 ores showed a significant improvement in the NgR-treated group relative to the control group (p < 0.0

174 tration of a soluble peptide fragment of the NgR (sNgR) that binds to and blocks all three NgR ligand

175 hus, delayed pharmacological blockade of the NgR promotes subacute stroke recovery by facilitating ax

176 sting that p75 is a signal transducer of the NgR-p75 receptor complex.

177 cells with mutated NgR demonstrates that the NgR C-terminal domain is required for inhibitory signali

178 genotype of the neurons, indicating that the NgR ligand-binding domain can act independent of NgR.

179 Subcutaneous treatment with the NgR antagonist peptide NEP1-40 (Nogo extracellular pepti

180 APP physically associates with the NgR.

181 Loss of any one of the NgRs results in an increase in synapse number in vitro,

182 gR (sNgR) that binds to and blocks all three NgR ligands can promote regeneration after brachial dors

183 bitor of neurite outgrowth that acts through NgR and its associated receptor complex.

184 Thus, NgR activation by Nogo-A involves multiple sites of inte

185 Thus, NgR is not essential for mediating inhibitory signals fr

186 Thus, NgR is partially responsible for limiting the regenerati

187 Thus, NgR(OMNI)-Fc may offer therapeutic opportunities followi

188 t MAG binds directly, with high affinity, to NgR.

189 ), which acts as a competitive antagonist to NgR for binding of inhibitory ligands; and 3) antagonizi

190 Also, MAG and Nogo66 compete for binding to NgR.

191 -specific domain in Amino-Nogo that binds to NgR with nanomolar affinity.

192 Binding of MAG to NgR-expressing cells is GPI dependent and sialic acid in

193 l-specific effects quantitatively similar to NgR blockers.

194 as additional physiologic roles unrelated to NgR binding.

195 Fusion of the two NgR-binding Nogo-A domains creates a ligand with substan

196 Overexpression of wild-type NgR blocked almost all regeneration from growth-sensitiz

197 A chimeric Nogo receptor variant (NgR(OMNI)) in which Cys(309)-Cys(336) is deleted and fol

198 In DRGNs, most of the MAG inhibition was via NgRs, evidenced by reversal of inhibition by phosphatidy

199 is upregulated to a moderate degree, whereas NgR levels are maintained at constant levels.

200 can form a functional receptor complex with NgR and LINGO-1 to mediate cellular responses to myelin

201 AG inhibits regeneration by interaction with NgR.

202 growth factors, specifically interacts with NgR.

203 The inverse correlation of Abeta levels with NgR levels within the brain may reflect regulation of Ab

204 e sharing extensive sequence similarity with NgR, two related proteins, NgR2 and NgR3, which we have

205 me animals received combination therapy with NgR(310)ecto-Fc plus rolipram, a cyclic adenosine monoph