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 ugh binding to myelin-associated inhibitors, NgRs contribute to the inhibition of axonal regeneration

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

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

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

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

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

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

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

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

68 1 is the founding member of the three-member NgR family, whereas Nogo-A (RTN4A) belongs to a four-mem

69 7 chick retinal ganglion cells with mutated NgR demonstrates that the NgR C-terminal domain is requi

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

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

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

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

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

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

76 rough interaction with its receptors, Nogo66/NgR.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

92 active ligand-binding soluble ectodomain of NgR.

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

94 are rendered MAG-sensitive by expression of NgR.

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

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

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

98 ligand-binding domain can act independent of NgR.

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

100 AFF/BlyS) may also be an important ligand of NgR during neuroinflammation.

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

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

103 Overexpression of NgR decreases Abeta production in neuroblastoma culture,

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

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

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

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

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

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

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

111 at concave side of the solenoid structure of NgR.

112 Here, we show a physiological role of NgRs in guiding commissural axons during early developme

113 es, many studies have focused on the role of NgRs, particularly NgR1, in axonal regeneration in the i

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

142 ogo-66) interacts with the Nogo-66 receptor (NgR).

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

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

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

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

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

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

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

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

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

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

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

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

155 phosphatidylinositol-anchored Nogo receptor (NgR).

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

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

158 ructurally, interact with the same receptor, NgR.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

173 The NgR glycosylphosphatidylinositol domain is not essential

174 The NgR ligand-binding domain promotes neurite outgrowth on

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

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

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

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

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

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

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

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

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

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

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

186 APP physically associates with the NgR.

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

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

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

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

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

192 Thus, NgR is partially responsible for limiting the regenerati

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

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

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

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

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

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

199 l-specific effects quantitatively similar to NgR blockers.

200 as additional physiologic roles unrelated to NgR binding.

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

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

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

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

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

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

207 AG inhibits regeneration by interaction with NgR.

208 growth factors, specifically interacts with NgR.

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

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

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