Genetic deletion of the Nogo receptor does not reduce neurite inhibition
            <i>in vitro</i>
            or promote corticospinal tract regeneration
            <i>in vivo</i>

Zheng, Binhai; Atwal, Jasvinder K.; Ho, Ching Lin; Case, Lauren C.; Xiao, He; García, K. Christopher; Steward, Oswald; Tessier‐Lavigne, Marc

doi:10.1073/pnas.0409026102

Cited by 253 publications

(255 citation statements)

References 23 publications

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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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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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“…As an example, NgR mRNA and protein are unevenly distributed in the adult CNS with some important regions lacking NgR (see Hunt et al, 2002a,b) and mechanisms other than Nogo/NgR interactions must explain the lack of axonal regeneration in these areas. In addition, using mice deficient in Nogo-A or NgR, some reports have shown axonal regeneration and marked behavioral improvement following SCI Kim et al, 2003Kim et al, , 2004, whereas other studies did not detect any differences when compared to their wild-type littermates (Zheng et al, 2003(Zheng et al, , 2005. Other recent reports have suggested a more complex role for Nogo other than associated with inhibition of axonal outgrowth (Jokic et al, 2005;He et al, 2004;Karnezis et al, 2004;Acevado et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat

Marklund

Fulp

Shimizu

et al. 2006

Experimental Neurology

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Axons show a poor regenerative capacity following traumatic central nervous system (CNS) injury, partly due to the expression of inhibitors of axonal outgrowth, of which Nogo-A is considered the most important. We evaluated the acute expression of Nogo-A, the Nogo-66 receptor (NgR) and the novel small proline-rich repeat protein 1A (SPRR1A, previously undetected in brain), following experimental lateral fluid percussion (FP) brain injury in rats. Immunofluorescence with antibodies against Nogo-A, NgR and SPRR1A was combined with antibodies against the neuronal markers NeuN and microtubule-associated protein (MAP)-2 and the oligodendrocyte marker RIP, while Western blot analysis was performed for Nogo-A and NgR. Brain injury produced a significant increase in Nogo-A expression in injured cortex, ipsilateral external capsule and reticular thalamus from days 1-7 post-injury (P < 0.05) compared to controls. Increased expression of Nogo-A was observed in both RIP-and NeuN positive (+) cells in the ipsilateral cortex, in NeuN (+) cells in the CA3 region of the hippocampus and reticular thalamus and in RIP (+) cells in white matter tracts. Alterations in NgR expression were not observed following traumatic brain injury (TBI). Brain injury increased the extent of SPRR1A expression in the ipsilateral cortex and the CA3 at all post-injury time-points in NeuN (+) cells. The marked increases in Nogo-A and SPRR1A in several important brain regions suggest that although inhibitors of axonal growth may be upregulated, the injured brain is also capable of expressing proteins promoting axonal outgrowth following TBI. KeywordsNogo-A; Nogo-66 receptor; Small proline-rich repeat protein 1A (SPRR1A); Traumatic brain injury; Oligodendrocytes

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“…Two groups independently generated and characterized NgR1 null mice. Both groups failed to observe enhanced axon regeneration in the CST of NgR1 mutants, an unexpected finding given that NgR1 can mediate the inhibitory effect of all three prototypical myelin inhibitors (Kim et al, 2004;Zheng et al, 2005). Interestingly, one group found enhanced regeneration of the raphespinal and rubrospinal fiber tracts and improved motor function after complete transection (Kim et al, 2004).…”

Section: Ngr1mentioning

confidence: 96%

“…However, in a neurite outgrowth assay, NgR1 deficient postnatal cerebellar postnatal granule neurons or dorsal root ganglion neurons are as inhibited as wild type neurons by immobilized myelin or Nogo-66 substrate (Zheng et al, 2005). Investigating the differential requirement for NgR1 in mediating the effect of myelin inhibitors in a growth cone collapse vs. neurite outgrowth assay might lead to important insight into the signaling mechanism of myelin inhibition.…”

Section: Ngr1mentioning

confidence: 99%

“…Investigating the differential requirement for NgR1 in mediating the effect of myelin inhibitors in a growth cone collapse vs. neurite outgrowth assay might lead to important insight into the signaling mechanism of myelin inhibition. Nevertheless, the ligand binding domain (LBD) of NgR1 promotes neurite outgrowth independent of the genotype of the neurons, that is, it promotes neurite growth from both wild type and NgR1-deficient neurons (Zheng et al, 2005). This result indicates that exogenous LBD of NgR1 can mask inhibitory epitopes that do not usually signal through endogenous NgR1 and/or other receptors are redundant with NgR1.…”

Section: Ngr1mentioning

confidence: 99%

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White matter inhibitors in CNS axon regeneration failure

Xie

Zheng

2008

Experimental Neurology

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Multiple lines of evidence have indicated that the inability of adult mammalian central nervous system (CNS) axons to regenerate after injury is partly due to the growth inhibitory property of central myelin. Three prototypical myelin-associated inhibitors of neurite outgrowth have been identified, including Nogo, myelin-associated glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgp). These inhibitory ligands, their receptors and signaling pathways are being intensively investigated for their roles in CNS axon regeneration failure. In addition, several members of the axon guidance molecules have been implicated in restricting CNS axon regeneration, some of which are expressed by mature oligodendrocytes. Here we review in vitro and in vivo studies of these molecules in neurite growth and in axon regeneration failure and discuss the implications of these studies. While the increasing number of potential axon regeneration inhibitors highlights the complexity of the restrictive CNS environment, it provides new windows of opportunity as well as new challenges for therapeutic development for spinal cord injury and related neurological conditions.

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Genetic deletion of the Nogo receptor does not reduce neurite inhibition in vitro or promote corticospinal tract regeneration in vivo

Cited by 253 publications

References 23 publications

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

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

Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat

White matter inhibitors in CNS axon regeneration failure

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