Blockade of Nogo-66, Myelin-Associated Glycoprotein, and Oligodendrocyte Myelin Glycoprotein by Soluble Nogo-66 Receptor Promotes Axonal Sprouting and Recovery after Spinal Injury

Li, Shuxin; Liu, Betty P.; Budel, Stephane; Li, Mingwei; Ji, Benxiu; Walus, Lee; Li, Weiwei; Jirik, Adrienna; Rabacchi, Sylvia A.; Choi, Eugene; Worley, Dane; Sah, Dinah W.Y.; Pepinsky, Blake; Lee, Daniel; Relton, Jane K.; Strittmatter, Stephen M.

doi:10.1523/jneurosci.2828-04.2004

Cited by 281 publications

(258 citation statements)

References 42 publications

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“…In these mice, axonal regeneration was increased compared with control animals, in line with the effects obtained by acute pharmacological treatments such as the anti-Nogo-A antibody infusion, the application of the soluble NgR1 decoy receptor, or Rho-A/Rho-associated protein kinase blocking agents. [43][44][45] The improved regeneration that we reported here for the optic nerve is in contrast with what has previously been observed in systemic, conventional KO mice. 29 We speculate that the lack of axonal regeneration improvement observed after optic nerve crush in the conventional, full KO mouse line may be due, at least in part, to the lack of neuronal Nogo-A expression.…”

Section: Discussioncontrasting

confidence: 99%

Cell type-specific Nogo-A gene ablation promotes axonal regeneration in the injured adult optic nerve

et al. 2014

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Nogo-A is a well-known myelin-enriched inhibitory protein for axonal growth and regeneration in the central nervous system (CNS). Besides oligodendrocytes, our previous data revealed that Nogo-A is also expressed in subpopulations of neurons including retinal ganglion cells, in which it can have a positive role in the neuronal growth response after injury, through an unclear mechanism. In the present study, we analyzed the opposite roles of glial versus neuronal Nogo-A in the injured visual system. To this aim, we created oligodendrocyte (Cnp-Cre þ / À xRtn4/Nogo-A flox/flox ) and neuron-specific (Thy1-Cre tg þ xRtn4 flox/flox ) conditional Nogo-A knock-out (KO) mouse lines. Following complete intraorbital optic nerve crush, both spontaneous and inflammation-mediated axonal outgrowth was increased in the optic nerves of the glia-specific Nogo-A KO mice. In contrast, neuron-specific deletion of Nogo-A in a KO mouse line or after acute gene recombination in retinal ganglion cells mediated by adeno-associated virus serotype 2.Cre virus injection in Rtn4 flox/flox animals decreased axon sprouting in the injured optic nerve. These results therefore show that selective ablation of Nogo-A in oligodendrocytes and myelin in the optic nerve is more effective at enhancing regrowth of injured axons than what has previously been observed in conventional, complete Nogo-A KO mice. Our data also suggest that neuronal Nogo-A in retinal ganglion cells could participate in enhancing axonal sprouting, possibly by cis-interaction with Nogo receptors at the cell membrane that may counteract trans-Nogo-A signaling. We propose that inactivating Nogo-A in glia while preserving neuronal Nogo-A expression may be a successful strategy to promote axonal regeneration in the CNS.

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Section: Discussioncontrasting

confidence: 99%

Cell type-specific Nogo-A gene ablation promotes axonal regeneration in the injured adult optic nerve

et al. 2014

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“…This can accomplished pharmacologically in rats via intrathecal cannula placement . Recent descriptions of intrathecal NgR(310)ecto-Fc treatment of rats and of mice lacking NgR protein support the conclusions of the current study Li et al, 2004).…”

Section: Discussionsupporting

confidence: 87%

Transgenic inhibition of Nogo-66 receptor function allows axonal sprouting and improved locomotion after spinal injury

Kim

Budel

et al. 2005

Molecular and Cellular Neuroscience

100

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Axon growth after spinal injury is thought to be limited in part by myelin-derived proteins that act via the Nogo-66 Receptor (NgR). To test this hypothesis, we sought to study recovery from spinal cord injury (SCI) after inhibiting NgR transgenically with a soluble function-blocking NgR fragment. Glial fibrillary acidic protein (gfap) gene regulatory elements were used to generate mice that secrete NgR(310)ecto from astrocytes. After mid-thoracic dorsal over-hemisection injury, gfap∷ngr(310)ecto mice exhibit enhanced raphespinal and corticospinal axonal sprouting into the lumbar spinal cord. Recovery of locomotion is improved in the gfap∷ngr(310)ecto mice. These data indicate that the NgR ligands, Nogo-66, MAG, and OMgp, play a role in limiting axonal growth in the injured adult CNS and that NgR(310)ecto might provide a therapeutic means to promote recovery from SCI.

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“…[2][3][4][46][47][48][49] During the past years, different therapies have been proposed that lead to axonal outgrowth after SCI such as SM-216289, 36 neurotrophic factors, 50 soluble Nogo receptors, 51 chondroitinase ABC 49 or cellular transplantation. 52 In particular, SM-216289, a small-molecule inhibitor, showed inhibition of Sema3A functions, including growth cone collapse and chemorepulsion of neurite extension.…”

Section: Discussionmentioning

confidence: 99%

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

et al. 2014

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Following spinal cord injury (SCI), semaphorin 3A (Sema3A) prevents axonal regeneration through binding to the neuropilin-1 (NRP-1)/PlexinA4 receptor complex. Here, we show that galectin-1 (Gal-1), an endogenous glycan-binding protein, selectively bound to the NRP-1/PlexinA4 receptor complex in injured neurons through a glycan-dependent mechanism, interrupts the Sema3A pathway and contributes to axonal regeneration and locomotor recovery after SCI. Although both Gal-1 and its monomeric variant contribute to de-activation of microglia, only high concentrations of wild-type Gal-1 (which co-exists in a monomer-dimer equilibrium) bind to the NRP-1/PlexinA4 receptor complex and promote axonal regeneration. Our results show that Gal-1, mainly in its dimeric form, promotes functional recovery of spinal lesions by interfering with inhibitory signals triggered by Sema3A binding to NRP-1/PlexinA4 complex, supporting the use of this lectin for the treatment of SCI patients.

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Blockade of Nogo-66, Myelin-Associated Glycoprotein, and Oligodendrocyte Myelin Glycoprotein by Soluble Nogo-66 Receptor Promotes Axonal Sprouting and Recovery after Spinal Injury

Cited by 281 publications

References 42 publications

Cell type-specific Nogo-A gene ablation promotes axonal regeneration in the injured adult optic nerve

Cell type-specific Nogo-A gene ablation promotes axonal regeneration in the injured adult optic nerve

Transgenic inhibition of Nogo-66 receptor function allows axonal sprouting and improved locomotion after spinal injury

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

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