Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Functions of Nogo proteins and their receptors in the nervous system

Key Points

  • The membrane protein Nogo-A is a major player in the neurite growth-inhibitory and regeneration-inhibitory effects exerted by myelin in the mammalian brain and spinal cord. In the injured CNS, neutralization or blockade of Nogo-A enhances regeneration, compensatory fibre sprouting and functional recovery. In the intact nervous system, a number of physiological functions of Nogo proteins have been recently discovered, as discussed in this Review.

  • Nogo proteins and the related reticulon (RTN)1-3 proteins consist of a highly conserved, 200-amino acid carboxy-terminal RTN domain and non-homologous amino-terminal extensions of various lengths. The neurite growth-inhibitory protein Nogo-A appeared in evolution for the first time in frogs and is present in all higher vertebrates. Two active sites are present; a Nogo-A-specific domain and a 66-amino acid domain that lies between the transmembrane and intramembrane parts of the RTN domain. Nogo-A is highly enriched in the nervous system, in oligodendrocytes and myelin at adult stages, and in neurons and precursor cells during development. The short proteins Nogo-B and Nogo-C are not inhibitory and occur in various tissues, including the nervous system.

  • Two binding sites are currently known for the Nogo-66 sequence, the Nogo receptor 1 (NgR1) and the membrane protein paired immunoglobulin-like receptor B (PIRB). Both receptors also interact with other ligands, however. The receptor for the Nogo-A specific active site remains to be characterized. Rho activation followed by destabilizing effects on the cytoskeleton are obligatory steps in the postreceptor signalling and effector pathway that leads to the collapse of neurite growth cones. Several additional proteins are associated with what is probably a multisubunit receptor complex for Nogo-A.

  • Nogo-B, by interaction with a Nogo-B receptor (NGBR), influences vascular endothelial cells and smooth muscle cells, which hyperproliferate after vascular lesions in Nogo-A and Nogo-B double knockout mice. The function of Nogo-C is currently still unknown.

  • During CNS development, Nogo-A and its receptors are expressed in cortical precursors and affect their migration. Many projection neurons in the central and peripheral nervous systems express Nogo-A during axonal outgrowth; its neutralization or knockout enhances axonal fasciculation and influences branching. NgR1 and the shorter Nogo forms also have guidance and fasciculation functions in zebrafish, a lower vertebrate.

  • In the adult CNS, oligodendrocyte and myelin Nogo-A suppresses the growth programme of adult neurons, probably by a retrograde action on the cell bodies. Locally, neurite growth is dampened by the growth cone collapsing actions of Nogo-A. Nogo-A thus acts as a stabilizer of the adult CNS neuronal network and wiring. Ablation of Nogo-A or NgR1 accordingly enhances plastic rearrangements of CNS connections, extending the so-called 'critical period' far into adult ages, for example, for visual cortex plasticity. The schizophrenia-like behaviour of Nogo-A knockout mice and the associations found between psychiatric disorders and mutations in the genes encoding Nogo or NgR1 may be based on similar functions.

  • In addition to its cell surface expression, high amounts of Nogo are also present intracellularly. In neurons, its interaction with β-secretase points to a role in the regulation of amyloid precursor protein (APP) processing. Manipulations of Nogo have indicated a structural role for Nogo in the endoplasmic reticulum (ER) and the nuclear membrane. Interactions with proteins involved in cell survival and apoptosis have also been observed.

  • Various approaches aimed at suppressing Nogo-A or NgR1 actions have been used following injury of the adult spinal cord or brain. Acute functional suppression and, with more variable effects, chronic genetic deletion enhance regenerative sprouting and growth of various CNS tract systems. In addition, spared fibre systems have shown enhanced compensatory sprouting; both these processes were associated with substantial improvements of the behavioural recovery of lost functions in rodents and monkeys. These results illustrate the important growth-suppressive role of Nogo-A in the adult mammalian CNS.

Abstract

The membrane protein Nogo-A was initially characterized as a CNS-specific inhibitor of axonal regeneration. Recent studies have uncovered regulatory roles of Nogo proteins and their receptors — in precursor migration, neurite growth and branching in the developing nervous system — as well as a growth-restricting function during CNS maturation. The function of Nogo in the adult CNS is now understood to be that of a negative regulator of neuronal growth, leading to stabilization of the CNS wiring at the expense of extensive plastic rearrangements and regeneration after injury. In addition, Nogo proteins interact with various intracellular components and may have roles in the regulation of endoplasmic reticulum (ER) structure, processing of amyloid precursor protein and cell survival.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Domains, localization, binding partners and signalling of Nogo proteins.
Figure 2: Common intracellular pathways but opposite effects of Nogo-A and neurotrophins.
Figure 3: Functions of Nogo-A in the developing and adult CNS.
Figure 4: Role of NgR or Nogo-A/Nogo-B in restricting the developmental plasticity in the visual cortex.

Similar content being viewed by others

References

  1. Schwab, M. E. Nogo and axon regeneration. Curr. Opin. Neurobiol. 14, 118–124 (2004).

    Article  CAS  PubMed  Google Scholar 

  2. Chen, M. S. et al. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen form monoclonal antibody IN-1. Nature 403, 434–439 (2000).

    Article  CAS  PubMed  Google Scholar 

  3. GrandPre, T., Nakamura, F., Vartanian, T. & Strittmatter, S. M. Identification of the Nogo inhibitor of axon regeneration as a reticulon protein. Nature 403, 439–444 (2000).

    Article  CAS  PubMed  Google Scholar 

  4. Oertle, T. et al. Nogo-A inhibits neurite outgrowth and cell spreading with three discrete regions. J. Neurosci. 23, 5393–5406 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Oertle, T. & Schwab, M. E. Nogo and its paRTNers. Trends Cell Biol. 13, 187–194 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Oertle, T., Huber, C., van der Putten, H. & Schwab, M. E. Genomic structure and functional characterisation of the promoters of human and mouse nogo/rtn4. J. Mol. Biol. 325, 299–323 (2003).

    Article  CAS  PubMed  Google Scholar 

  7. Li, M. & Song, J. The N- and C-termini of the human Nogo molecules are intrinsically unstructured: bioinformatics, CD, NMR characterization, and functional implications. Proteins 68, 100–108 (2007).

    Article  CAS  PubMed  Google Scholar 

  8. Dodd, D. A. et al. Nogo-A, -B and -C are found on the cell surface and interact together in many different cell types. J. Biol. Chem. 280, 12494–12502 (2005).

    Article  CAS  PubMed  Google Scholar 

  9. Oertle, T., Klinger, M., Stuermer, C. A. O. & Schwab, M. E. A reticular rhapsody: phylogenic evolution and nomenclature of the RTN/Nogo gene family. FASEB J. 17, 1238–1247 (2003).

    Article  CAS  PubMed  Google Scholar 

  10. Diekmann, H. et al. Analysis of the reticulon gene family demonstrates the absence of the neurite growth inhibitor Nogo-A in fish. Mol. Biol. Evol. 22, 1635–1648 (2005).

    Article  CAS  PubMed  Google Scholar 

  11. Schweigreiter, R. The natural history of the myelin-derived nerve growth inhibitor Nogo-A. Neuron Glia Biol. 4, 83–89 (2008).

    Article  PubMed  Google Scholar 

  12. Klinger, M. et al. Identification of two nogo/rtn4 genes and analysis of Nogo-A expression in Xenopus laevis. Mol. Cell. Neurosci. 25, 205–216 (2004).

    Article  CAS  PubMed  Google Scholar 

  13. Ferretti, P., Zhang, F. & O'Neill, P. Changes in spinal cord regenerative ability through phylogenesis and development: lessons to be learnt. Dev. Dyn. 226, 245–256 (2003).

    Article  PubMed  Google Scholar 

  14. Fournier, A. E., GrandPre, T. & Strittmatter, S. M. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 409, 341–346 (2001).

    Article  CAS  PubMed  Google Scholar 

  15. Hu, F. et al. Nogo-A interacts with the Nogo-66 receptor throuth multiple sites to create an isoform-selective subnanomolar agonist. J. Neurosci. 25 5298–5304 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. GrandPre, T., Li, S. & Strittmatter, S. M. Nogo-66 receptor antagonist peptide promotes axonal regeneration. Nature 417, 547–551 (2002).

    Article  CAS  PubMed  Google Scholar 

  17. Domeniconi, M. et al. Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron 35, 283–290 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Wang, K. C., Kim, J. A., Sivasankaran, R., Segal, R. & He, Z. p75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature 420, 74–78 (2002).

    Article  CAS  PubMed  Google Scholar 

  19. Venkatesh, K. et al. The Nogo-66 receptor homolog NgR2 is a sialic acid-dependent receptor selective for myelin-associated glycoprotein. J. Neurosci. 25, 808–822 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Park, J. H. et al. Alzheimer precursor protein interaction with the Nogo-66 receptor reduces amyloid-β plaque deposition. J. Neurosci. 26, 1386–1395 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhang, L. et al. Identification of BLyS (B lymphocyte stimulator), a non-myelin-associated protein, as a functional ligand for Nogo-66 receptor. J. Neurosci. 29, 6348–6352 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Thomas, R. et al. LGI1 is a Nogo receptor 1 ligand that antagonizes myelin-based growth inhibition. J. Neurosci. 30, 6607–6612 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Atwal, J. K. et al. PirB is a functional receptor for myelin inhibitors of axonal regeneration. Science 322, 967–970 (2008).

    Article  CAS  PubMed  Google Scholar 

  24. Fournier, A. E., Gould, G. C., Liu, B. P. & Strittmatter, S. M. Truncated soluble Nogo receptor binds Nogo-66 and blocks inhibition of axon growth by myelin. J. Neurosci. 22, 8876–8883 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chivatakarn, O., Kaneko, S., He, Z., Tessier-Lavigne, M. & Giger, R. J. The Nogo-66 receptor NgR1 is required only for the acute growth cone-collapsing but not the chronic growth-inhibitory actions of myelin inhibitors. J. Neurosci. 27, 7117–7124 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Takei, Y. Phosphorylation of Nogo receptors suppresses Nogo signaling, allowing neurite regeneration. Sci. Signal 2, ra14 (2009).

    Article  CAS  PubMed  Google Scholar 

  27. Lee, J. K., Kim, J. E., Sivula, M. & Strittmatter, S. M. Nogo receptor antagonism promotes stroke recovery by enhancing axonal plasticity. J. Neurosci. 24, 6209–6217 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kim, J. E., Liu, B. P., Park, H. J. & Strittmatter, S. M. Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury. Neuron 44, 439–451 (2004).

    Article  CAS  PubMed  Google Scholar 

  29. Zheng, B. et al. Genetic deletion of the Nogo receptor does not reduce neurite inhibition in vitro or promote corticospinal tract regeneration in vivo. Proc. Natl Acad. Sci. USA 102, 1205–1210 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fischer, D., He, Z. & Benowitz, L. I. Counteracting the Nogo receptor enhances optic nerve regeneration if retinal ganglion cells are in an active growth state. J. Neurosci. 24, 1651 (2004).

    Google Scholar 

  31. Syken, J., Grandpre, T., Kanold, P. O. & Shatz, C. J. PirB restricts ocular-dominance plasticity in visual cortex. Science 313, 1795–1800 (2006).

    Article  CAS  PubMed  Google Scholar 

  32. McGee, A. W., Yang, Y., Fischer, Q. S., Daw, N. W. & Strittmatter, S. M. Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor. Science 309, 2222–2226 (2006). This paper shows that the developmental plasticity in the well-known paradigm of visual cortex ocular dominance columns is restricted at the end of the critical period by mechanisms involving NgR, and Nogo-A and Nogo-B.

    Article  CAS  Google Scholar 

  33. Nash, M., Pribiag, H., Fournier, A. E. & Jacobson, C. Central nervous system regeneration inhibitors and their intracellular substrates. Mol. Neurobiol. 40, 224–235 (2009). A recent review on the intracellular pathways, in particular RHOA signalling, that have key roles in Nogo signalling.

    Article  CAS  PubMed  Google Scholar 

  34. Spencer, T., Domeniconi, M., Cao, Z. & Filbin, M. T. New roles for old proteins in adult CNS axonal regeneration. Curr. Opin. Neurobiol. 13, 133–139 (2003).

    Article  CAS  PubMed  Google Scholar 

  35. Yiu, G. & He, Z. Glial inhibition of CNS axon regeneration. Nature Rev. Neurosci. 7, 617–627 (2006).

    Article  CAS  Google Scholar 

  36. Shao, Z. et al. TAJ/TROY, an orphan TNR receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration. Neuron 45, 353–359 (2005).

    Article  CAS  PubMed  Google Scholar 

  37. Park, J. B. et al. A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors. Neuron 45, 345–351 (2005).

    Article  CAS  PubMed  Google Scholar 

  38. Mi, S. et al. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nature Neurosci. 7, 221–228 (2004).

    Article  CAS  PubMed  Google Scholar 

  39. Ji, B. et al. LINGO-1 antagonist promotes functional recovery and axonal sprouting after spinal cord injury. Mol. Cell. Neurosci. 33, 311–320 (2006).

    Article  CAS  PubMed  Google Scholar 

  40. Lv, J. et al. Passive immunization with LINGO-1 polyclonal antiserum afforded neuroprotection and promoted functional recovery in a rat model of spinal cord injury. Neuroimmunomodulation 17, 270–278 (2010).

    Article  CAS  PubMed  Google Scholar 

  41. Okafuji, T. & Tanaka, H. Expression patern of LINGO-1 in the developing nervous system of the chick embryo. Gene Expr. Patterns 6, 57–62 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Barrette, B., Vallieres, N., Dube, M. & Lacroix, S. Expression profile of receptors for myelin-associated inhibitors of axonal regeneration in the intact and injured mouse central nervous system. Mol. Cell. Neurosci. 34, 519–538 (2007).

    Article  CAS  PubMed  Google Scholar 

  43. Hu, F. & Strittmatter, S. M. The N-terminal domain of Nogo-A inhibits cell adhesion and axonal outgrowth by an integrin-specific mechanism. J. Neurosci. 28, 1262–1269 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Koprivica, V. et al. EGFR activation mediates inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans. Science 310, 106–110 (2005).

    Article  CAS  PubMed  Google Scholar 

  45. Grunewald, E., Kinnell, H. L., Porteous, D. J. & Thomson, P. A. GPR50 interacts with neuronal NOGO-A and affects neurite outgrowth. Mol. Cell. Neurosci. 42, 363–371 (2009).

    Article  CAS  PubMed  Google Scholar 

  46. Chao, M. V. Neurotrophins and their receptors: a convergence point for many signalling pathways. Nature Rev. Neurosci. 4, 299–309 (2003).

    Article  CAS  Google Scholar 

  47. Inestrosa, N. C. & Arenas, E. Emerging roles of Wnts in the adult nervous system. Nature Rev. Neurosci. 11, 77–86 (2010).

    Article  CAS  Google Scholar 

  48. Rajasekharan, S. & Kennedy, T. E. The netrin protein family. Genome Biol. 10, 239 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Jackson, R. E. & Eickholt, B. J. Semaphorin signalling. Curr. Biol. 19, R504–R507 (2009).

    Article  CAS  PubMed  Google Scholar 

  50. Miao, R. Q. et al. Identification of a receptor necessary for Nogo-B stimulated chemotaxis and morphogenesis of endothelial cells. Proc. Natl Acad. Sci. USA 103, 10997–11002 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Acevedo, L. et al. A new role for Nogo as a regulator of vascular remodeling. Nature Med. 10, 382–388 (2004). The first demonstration of a role of Nogo proteins, in particular Nogo-B, in vascular endothelial cells and smooth muscle cells, and in blood vessel repair.

    Article  CAS  PubMed  Google Scholar 

  52. Harrison, K. D. et al. Nogo-B receptor stabilizes Niemann-Pick type C2 protein and regulates intracellular cholesterol trafficking. Cell Metab. 10, 208–218 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Fournier, A. E., Takizawa, B. T. & Strittmatter, S. M. Rho kinase inhibition enhances axonal regeneration in the injured CNS. J. Neurosci. 23, 1416–1423 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lehmann, M. et al. Inactivation of Rho signaling pathway promotes CNS axon regeneration. J. Neurosci. 19, 7537–7547 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Niederost, B., Oertle, T., Fritsche, J., McKinney, R. A. & Bandtlow, C. E. Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Rac1. J. Neurosci. 22, 10368–10376 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kubo, T., Yamaguchi, A., Iwata, N. & Yamashita, T. The therapeutic effects of Rho-ROCK inhibitors on CNS disorders. Ther. Clin. Risk Manag. 4, 605–615 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Joset, A., Dodd, D. A., Halegoua, S. & Schwab, M. E. Pincher-generated Nogo-A endosomes mediate growth cone collapse and retrograde signaling. J. Cell Biol. 188, 271–285 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Deng, K. et al. Overcoming amino-Nogo-induced inhibition of cell spreading and neurite outgrowth by 12-O-tetradecanoylphorbol-13-acetate-type tumor promoters. J. Biol. Chem. 285, 6425–6433 (2010).

    Article  CAS  PubMed  Google Scholar 

  59. Bandtlow, C. E., Schmidt, M. F., Hassinger, T. D., Schwab, M. E. & Kater, S. B. Role of intracellular calcium in NI-35-evoked collapse of neuronal growth cones. Science 259, 80–83 (1993).

    Article  CAS  PubMed  Google Scholar 

  60. Wong, S. T. et al. A p75 NTR and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein. Nature Neurosci. 5, 1302–1308 (2002).

    Article  CAS  PubMed  Google Scholar 

  61. Sivasankaran, R. et al. PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration. Nature Neurosci. 7, 261–268 (2004).

    Article  CAS  PubMed  Google Scholar 

  62. Wang, B. et al. Nogo-66 promotes the differentiation of neural progenitors into astroglial lineage cells through mTOR–STAT3 pathway. PLoS ONE 3, e1856 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Gao, Y. et al. Nogo-66 regulates nanog expression through stat3 pathway in murine embryonic stem cells. Stem Cells Dev. 19, 53–60 (2010).

    Article  CAS  PubMed  Google Scholar 

  64. Hannila, S. S. & Filbin, M. T. The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury. Exp. Neurol. 209, 321–332 (2008).

    Article  CAS  PubMed  Google Scholar 

  65. Yamashita, T. & Tohyama, M. The p75 receptor acts as a displacement factor that releases Rho from Rho–GDI. Nature Neurosci. 6, 461–467 (2003).

    Article  CAS  PubMed  Google Scholar 

  66. Hsieh, S. H. K., Ferraro, G. B. & Fournier, A. E. Myelin-associated inhibitors regulate cofilin phosphorylation and neuronal inhibition through LIM kinase and slingshot phosphatase. J. Neurosci. 26, 1006–1015 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Montani, L. et al. Neuronal Nogo-A modulates growth cone motility via Rho-GTP/LIMK1/cofilin in the unlesioned adult nervous system. J. Biol. Chem. 284, 10793–10807 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Cowan, C. W. et al. Vav family GEFs link activated Ephs to endocytosis and axon guidance. Neuron 46, 205–217 (2005).

    Article  CAS  PubMed  Google Scholar 

  69. Ibanez, C. F. Message in a bottle: long-range retrograde signaling in the nervous system. Trends Cell Biol. 17, 519–528 (2007).

    Article  CAS  PubMed  Google Scholar 

  70. Huber, A. B., Weinmann, O., Brösamle, C., Oertle, T. & Schwab, M. E. Patterns of Nogo mRNA and protein expression in the developing and adult rat and after CNS lesions. J. Neurosci. 22, 3553–3567 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Wang, X. et al. Localization of Nogo-A and Nogo-66 receptor proteins at sites of axon-myelin and synaptic contact. J. Neurosci. 22, 5505–5515 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. O'Neill, P., Whalley, K. & Ferretti, P. Nogo and Nogo-66 receptor in human and chick: implications for development and regeneration. Dev. Dyn. 231, 109–121 (2004).

    Article  CAS  PubMed  Google Scholar 

  73. Caltharp, S. et al. Nogo-A induction and localization during chick brain development indicate a role disparate from neurite outgrowth inhibition. BMC Dev. Biol. 7, 32 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Mingorance-Le Meur, A., Zheng, B., Soriano, E. & Del Rio, J. A. Involvement of the myelin-associated inhibitor Nogo-A in early cortical development and neuronal maturation. Cereb Cortex 17, 2375–2386 (2007).

    Article  PubMed  Google Scholar 

  75. Mathis, C., Schroter, A., Thallmair, M. & Schwab, M. E. Nogo-A regulates neural precursor migration in the embryonic mouse cortex. Cereb Cortex 20, 2380–2390 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Wang, J., Chan, C. K., Taylor, J. S. & Chan, S. O. Localization of Nogo and its receptor in the optic pathway of mouse embryos. J. Neurosci. Res. 86, 1721–1733 (2008).

    Article  CAS  PubMed  Google Scholar 

  77. Wang, J., Wang, L., Zhao, H. & Chan, S. O. Localization of an axon growth inhibitory molecule Nogo and its receptor in the spinal cord of mouse embryos. Brain Res. 1306, 8–17 (2010).

    Article  CAS  PubMed  Google Scholar 

  78. Mingorance, A. et al. Regulation of Nogo and Nogo receptor during the development of the entorhino-hippocampal pathway and after adult hippocampal lesions. Mol. Cell Neurosci. 26, 34–49 (2004).

    Article  CAS  PubMed  Google Scholar 

  79. Wang, J., Chan, C. K., Taylor, J. S. & Chan, S. O. The growth-inhibitory protein Nogo is involved in midline routing of axons in the mouse optic chiasm. J. Neurosci. Res. 86, 2581–2590 (2008).

    Article  CAS  PubMed  Google Scholar 

  80. Josephson, A., Widenfalk, J., Widmer, H. W., Olson, L. & Spenger, C. Nogo mRNA expression in adult and fetal human and rat nervous tissue and in weight drop injury. Exp. Neurol. 169, 319–328 (2001).

    Article  CAS  PubMed  Google Scholar 

  81. Richard, M. et al. Neuronal expression of Nogo-A mRNA and protein during neurite outgrowth in the developing rat olfacotry system. Europ. J. Neurosci. 22, 2145–2158 (2005).

    Article  Google Scholar 

  82. Hunt, D., Coffin, R. S., Prinjha, R. K., Campbell, G. & Anderson, P. N. Nogo-A expression in the intact and injured nervous system. Mol. Cell Neurosci. 24, 1083–1102 (2003).

    Article  CAS  PubMed  Google Scholar 

  83. Meier, S. et al. Molecular analysis of Nogo expression in the hippocampus during development and following lesion and seizure. FASEB J. 17, 1153–1155 (2003).

    Article  CAS  PubMed  Google Scholar 

  84. Lee, H. et al. Synaptic function for the Nogo-66 receptor NgR1: regulation of dendritic spine morphology and activity-dependent synaptic strength. J. Neurosci. 28, 2753–2765 (2008). The first comprehensive analysis of Nogo-A and its receptor components localized at synapses, and the possible role of NgR1 in synaptic plasticity

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Liu, Y. Y., Jin, W. L., Liu, H. L. & Ju, G. Electron. microscopic localization of Nogo-A at the postsynaptic active zone of the rat. Neurosci. Lett. 346, 153–156 (2003).

    Article  CAS  PubMed  Google Scholar 

  86. Fry, E. J., Ho, C. & David, S. A role for Nogo receptor in macrophage clearance from injured peripheral nerve. Neuron 53, 649–662 (2007).

    Article  CAS  PubMed  Google Scholar 

  87. David, S., Fry, E. J. & Lopez-Vales, R. Novel roles for Nogo receptor in inflammation and disease. Trends Neurosci. 31, 221–226 (2008).

    Article  CAS  PubMed  Google Scholar 

  88. Pool, M. et al. Myelin regulates immune cell adhesion and motility. Exp. Neurol. 217, 371–377 (2009).

    Article  CAS  PubMed  Google Scholar 

  89. Bullard, T. A. et al. Identification of Nogo as a novel indicator of heart failure. Physiol. Genomics 32, 182–189 (2008).

    Article  CAS  PubMed  Google Scholar 

  90. Yu, J. et al. Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair. Proc. Natl Acad. Sci. USA 106, 17511–17516 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Magnusson, C., Svensson, A., Christerson, U. & Tagerud, S. Denervation-induced alterations in gene expression in mouse skeletal muscle. Eur. J. Neurosci. 21, 577–580 (2005).

    Article  PubMed  Google Scholar 

  92. Jokic, N. et al. Nogo expression in muscle correlates with amyotrophic lateral sclerosis severity. Annals Neurology 57, 553–556 (2005).

    Article  CAS  Google Scholar 

  93. Tozaki, H., Kawasaki, T., Takagi, Y. & Hirata, T. Expression of Nogo protein by growing axons in the developing nervous system. Molec. Brain Res. 104, 111–119 (2002).

    Article  CAS  PubMed  Google Scholar 

  94. Petrinovic, M. M. et al. Neuronal Nogo-A regulates neurite fasciculation, branching and extension in the developing nervous system. Development 137, 2539–2550 (2010). Using antibodies against Nogo-A or NgR as well as using Nogo-A knockout mice, this paper shows a role of Nogo-A expressed by developing neurons in neurite fasciculation and branching in vitro , and in chicken and mouse embryos.

    Article  CAS  PubMed  Google Scholar 

  95. Schwab, M. E. & Schnell, L. Channelling of developing rat corticospinal tract axons by myelin-associated neurite growth inhibitors. J. Neurosci. 11, 709–722 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Schwab, M. E. Nerve fiber regeneration after traumatic lesions of the CNS; progress and problems. Phil. Trans. R. Soc. B 331, 303–306 (1991).

    Article  CAS  PubMed  Google Scholar 

  97. Abdesselem, H., Shypitsyna, A., Solis, G. P., Bodrikov, V. & Stuermer, C. A. No Nogo-66- and NgR-mediated inhibition of regenerating axons in the zebrafish optic nerve. J. Neurosci. 29, 15489–15498 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Klinger, M. et al. Identification of Nogo-66 receptor (NgF) and homologous genes in fish. Mol. Biol. Evol. 21, 76–85 (2004).

    Article  CAS  PubMed  Google Scholar 

  99. Brosamle, C. & Halpern, M. E. Nogo–Nogo receptor signalling in PNS axon outgrowth and pathfinding. Mol. Cell Neurosci. 40, 401–409 (2009).

    Article  CAS  PubMed  Google Scholar 

  100. O'Brien, G. S. et al. Developmentally regulated impediments to skin reinnervation by injured peripheral sensory axon terminals. Curr. Biol. 19, 2086–2090 (2009). This paper shows that zebrafish embryos express short Nogo forms as well as NgR, which play a part in neurite growth and target reinnervation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Pernet, V., Joly, S., Christ, F., Dimou, L. & Schwab, M. E. Nogo-a and myelin-associated glycoprotein differently regulate oligodendrocyte maturation and myelin formation. J. Neurosci. 28, 7435–7444 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Mi, S. et al. LINGO-1 negatively regulates myelination by oligodendrocytes. Nature Neurosci. 8, 745–751 (2005).

    Article  CAS  PubMed  Google Scholar 

  103. Caroni, P. & Schwab, M. E. Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J. Cell Biol. 106, 1281–1288 (1988).

    Article  CAS  PubMed  Google Scholar 

  104. Caroni, P. & Schwab, M. E. Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron 1, 85–96 (1988). One of three papers published in 1988 showing that CNS myelin is inhibitory for neurite growth, that a high molecular weight myelin protein ('NI-250', later called Nogo-A) is a key component of this activity and that it can be neutralized by antibodies. One of these antibodies was shown 2 years later to enhance long-distance regeneration in the injured rat spinal cord (see also references 103 and 105).

    Article  CAS  PubMed  Google Scholar 

  105. Schwab, M. E. & Caroni, P. Oligodendrocytes and CNS myelin are nonpermissive substrates for neurite growth and fibroblast spreading in vitro. J. Neurosci. 8, 2381–2393 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Maffei, A. & Turrigiano, G. The age of plasticity: developmental regulation of synaptic plasticity in neocortical microcircuits. Prog. Brain Res. 169, 211–223 (2008).

    Article  PubMed  Google Scholar 

  107. Hooks, B. M. & Chen, C. Critical periods in the visual system: changing views for a model of experience-dependent plasticity. Neuron 56, 312–326 (2007).

    Article  CAS  PubMed  Google Scholar 

  108. Schwegler, G., Schwab, M. E. & Kapfhammer, J. P. Increased collateral sprouting of primary afferents in the myelin-free spinal cord. J. Neurosci. 15, 2756–2767 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Kapfhammer, J. P. & Schwab, M. E. Inverse pattern of myelination and GAP-43 expression in the adult CNS: neurite growth inhibitors as regulators of neuronal plasticity? J. Comp. Neurol. 340, 194–206 (1994).

    Article  CAS  PubMed  Google Scholar 

  110. Craveiro, L. M. et al. Neutralization of the membrane protein Nogo-A enhances growth and reactive sprouting in established organotypic hippocampal slice cultures. Eur. J. Neurosci. 28, 1808–1824 (2008).

    Article  PubMed  Google Scholar 

  111. Park, K. J., Grosso, C. A., Aubert, I., Kaplan, D. R. & Miller, F. D. p75NTR-dependent, myelin-mediated axonal degeneration regulates neural connectivity in the adult brain. Nature Neurosci. 13, 559–566 (2010).

    Article  CAS  PubMed  Google Scholar 

  112. Aloy, E. M. et al. Synaptic destabilization by neuronal Nogo-A. Brain Cell Biol. 35, 137–156 (2006).

    Article  CAS  PubMed  Google Scholar 

  113. Karlen, A. et al. Nogo receptor 1 regulates formation of lasting memories. Proc. Natl Acad. Sci. USA 106, 20476–20481 (2009). The first demonstration that NgR is linked to specific aspects of memory in vivo.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Lai, K. O. & Ip, N. Y. Synapse development and plasticity: roles of ephrin/Eph receptor signaling. Curr. Opin. Neurobiol. 19, 275–283 (2009).

    Article  CAS  PubMed  Google Scholar 

  115. Yoshihara, Y., De Roo, M. & Muller, D. Dendritic spine formation and stabilization. Curr. Opin. Neurobiol. 19, 146–153 (2009).

    Article  CAS  PubMed  Google Scholar 

  116. Pasterkamp, R. J. & Giger, R. J. Semaphorin function in neural plasticity and disease. Curr. Opin. Neurobiol. 19, 263–274 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Willi, R. et al. Constitutive genetic deletion of the growth regulator Nogo-A induces schizophrenia-related endophenotypes. J. Neurosci. 30, 556–567 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Novak, G., Kim, D., Seeman, P. & Tallerico, T. Schizophrenia and Nogo: elevated mRNA in cortex, in high prevalence of a homozygous CAA insert. Molecular Brain Res. 107, 183–189 (2002).

    Article  CAS  Google Scholar 

  119. Tan, E. C., Chong, S. A., Wang, H., Lim, E. C. P. & Teo, Y. Y. Gender-specific association of insertion/deletoin polymorphisms in the nogo gene and chronic schizophrenia. Molec. Brain Res. 139 212–216 (2005).

    Article  CAS  PubMed  Google Scholar 

  120. Sinibaldi, L. et al. Mutations of the Nogo-66 receptor (RTN4R) gene in schizophrenia. Hum. Mutat. 24, 534–535 (2004).

    Article  PubMed  CAS  Google Scholar 

  121. Hsu, R. et al. Nogo Receptor 1 (RTN4R) as a candidate gene for schizophrenia: analysis using human and mouse genetic approaches. PLoS ONE 2, e1234 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. Budel, S. et al. Genetic variants of Nogo-66 receptor with possible association to schizophrenia block myelin inhibition of axon growth. J. Neurosci. 28, 13161–13172 (2008). Some families affected with psychiatric diseases show mutations in NgR1 that affect its interaction with Nogo-66. Knock-in mice show weak schizophrenia-like phenotypes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Lewis, D. A. & Levitt, P. Schizophrenia as a disorder of neurodevelopment. Annu. Rev. Neurosci. 25, 409–432 (2002).

    Article  CAS  PubMed  Google Scholar 

  124. Teng, F. Y. & Tang, B. L. Cell autonomous function of Nogo and reticulons: the emerging story at the endoplasmic reticulum. J. Cell Physiol. 216, 303–308 (2008).

    Article  CAS  PubMed  Google Scholar 

  125. He, W. et al. Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation. Nature Med. 10, 959–965 (2004). The first demonstration that Rtn proteins, including Nogo, interact with BACE, suggesting that Nogo proteins could be physiological regulators of BACE activity and amyloid production.

    Article  CAS  PubMed  Google Scholar 

  126. Murayama, K. S. et al. Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability to produce amyloid beta-protein. Eur. J. Neurosci. 24, 1237–1244 (2006).

    Article  PubMed  Google Scholar 

  127. He, W. et al. Mapping of interaction domains mediating binding between BACE1 and RTN/Nogo proteins. J. Mol. Biol. 363, 625–634 (2006).

    Article  CAS  PubMed  Google Scholar 

  128. Park, J.H. et al. Alzheimer precursor protein interaction with the Nogo-66 receptor reduces amyloid-beta plaque deposition. J. Neurosci. 26, 1386–1395 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Masliah, E. et al. Genetic deletion of Nogo/Rtn4 ameliorates behavioral and neuropathological outcomes in amyloid precursor protein transgenic mice. Neuroscience 169, 488–494 (2010).

    Article  CAS  PubMed  Google Scholar 

  130. Gil, V. et al. Nogo-A expression in the human hippocampus in normal aging and in Alzheimer disease. J. Neuropathol. Exp. Neurol. 65, 433–444 (2006).

    Article  CAS  PubMed  Google Scholar 

  131. Cheatwood, J. L., Emerick, A. J., Schwab, M. E. & Kartje, G. L. Nogo-A expression after focal ischemic stroke in the adult rat. Stroke 39, 2091–2098 (2008).

    Article  CAS  PubMed  Google Scholar 

  132. Yang, Y. S., Harel, N. Y. & Strittmatter, S. M. Reticulon-4A (Nogo-A) redistributes protein disulfide isomerase to protect mice from SOD1-dependent amyotrophic lateral sclerosis. J. Neurosci. 29, 13850–13859 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Tagami, S., Eguchi, Y., Kinoshita, M., Takeda, M. & Tsujimoto, Y. A novel protein, RTN-xs, interacts with both Bcl-xL, and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity. Oncogene 19, 5736–5746 (2000).

    Article  CAS  PubMed  Google Scholar 

  134. Wan, Q. et al. Reticulon 3 mediates Bcl-2 accumulation in mitochondria in response to endoplasmic reticulum stress. Apoptosis 12, 319–328 (2007).

    Article  CAS  PubMed  Google Scholar 

  135. Li, Q. et al. Link of a new type of apoptosis-inducing gene ASY/Nogo-B to human cancer. Oncogene 20, 3929–3936 (2001).

    Article  CAS  PubMed  Google Scholar 

  136. Oertle, T., Merkler, D. & Schwab, M. E. Do cancer cells die because of Nogo-B? Oncogene 22, 1390–1399 (2003).

    Article  CAS  PubMed  Google Scholar 

  137. Voeltz, G. K., Prinz, W. A., Shibata, Y., Rist, J. M. & Rapoport, T. A. A class of membrane proteins shaping the tubular endoplasmic reticulum. Cell 124, 573–586 (2006). A demonstration of the role of Nogo proteins in structuring specific parts of the ER and its interaction with other ER membrane proteins that induce membrane curvature.

    Article  CAS  PubMed  Google Scholar 

  138. Kiseleva, E., Morozova, K. N., Voeltz, G. K., Allen, T. D. & Goldberg, M. W. Reticulon 4a/Nogo-A locates to regions of high membrane curvature and may have a role in nuclear envelope growth. J. Struct. Biol. 160, 224–235 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Anderson, D. J. & Hetzer, M. W. Reshaping of the endoplasmic reticulum limits the rate for nuclear envelope formation. J. Cell Biol. 182, 911–924 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Shibata, Y. et al. The reticulon and DP1/Yop1p proteins form immobile oligomers in the tubular endoplasmic reticulum. J. Biol. Chem. 283, 18892–18904 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Simonen, M. et al. Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury. Neuron 38, 201–211 (2003).

    Article  CAS  PubMed  Google Scholar 

  142. Gonzenbach, R. R. & Schwab, M. E. Disinhibition of neurite growth to repair the injured adult CNS: focusing on Nogo. Cell. Mol. Life Sci. 65, 161–176 (2008). A review summarizing the various methods of Nogo-A blockade and its consequences for the treatment of spinal cord and brain injuries.

    Article  CAS  PubMed  Google Scholar 

  143. Rossignol, S., Schwab, M., Schwartz, M. & Fehlings, M. G. Spinal cord injury: time to move? J. Neurosci. 27, 11782–11792 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Xie, F. & Zheng, B. White matter inhibitors in CNS axon regeneration failure. Exp. Neurol. 209, 302–312 (2008).

    Article  CAS  PubMed  Google Scholar 

  145. Rowland, J. W., Hawryluk, G. W., Kwon, B. & Fehlings, M. G. Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg. Focus 25, e2 (2008).

    Article  PubMed  Google Scholar 

  146. Cheatwood, J. L., Emerick, A. J. & Kartje, G. L. Neuronal plasticity and functional recovery after ischemic stroke. Top. Stroke Rehabil. 15, 42–50 (2008).

    Article  PubMed  Google Scholar 

  147. Liu, B. P., Cafferty, W. B., Budel, S. O. & Strittmatter, S. M. Extracellular regulators of axonal growth in the adult central nervous system. Phil. Trans. R. Soc. Lond. B 361, 1593–1610 (2006).

    Article  CAS  Google Scholar 

  148. Fouad, K., Klusman, I. & Schwab, M. E. Regenerating corticospinal fibers in the marmoset (Callitrix jacchus) after spinal cord lesion and treatment with the anti-Nogo-A antibody IN-1. Eur. J. Neurosci. 20, 2479–2482 (2004).

    Article  CAS  PubMed  Google Scholar 

  149. Freund, P. et al. Nogo-A-specific antibody treatment enhances sprouting and functional recovery after cervical lesion in adult primates. Nature Med. 12, 790–792 (2006).

    Article  CAS  PubMed  Google Scholar 

  150. Freund, P. et al. Anti-Nogo-A antibody treatment promotes recovery of manual dexterity after unilateral cervical lesion in adult primates--re-examination and extension of behavioral data. Eur. J. Neurosci. 29, 983–996 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Barton, W. A. et al. Structure and axon outgrowth inhibitor binding of the Nogo-66 receptor and related proteins. EMBO J. 22, 3291–3302 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Gordon, M. D. & Nusse, R. Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J. Biol. Chem. 281, 22429–22433 (2006).

    Article  CAS  PubMed  Google Scholar 

  153. Teng, K. K., Felice, S., Kim, T. & Hempstead, B. L. Understanding proneurotrophin actions: Recent advances and challenges. Dev. Neurobiol. 70, 350–359 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Moore, S. W., Tessier-Lavigne, M. & Kennedy, T. E. Netrins and their receptors. Adv. Exp. Med. Biol. 621, 17–31 (2007).

    Article  PubMed  Google Scholar 

  155. Ly, A. et al. DSCAM is a netrin receptor that collaborates with DCC in mediating turning responses to netrin-1. Cell 133, 1241–1254 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Carmeliet, P. & Tessier-Lavigne, M. Common mechanisms of nerve and blood vessel wiring. Nature 436, 193–200 (2005).

    Article  CAS  PubMed  Google Scholar 

  157. Coon, H. et al. Evidence for a chromosome 2p13–14 schizophrenia susceptibility locus in families from Palau, Micronesia. Mol. Psychiatry 3, 521–527 (1998).

    Article  CAS  PubMed  Google Scholar 

  158. Liu, H. et al. Genetic variation in the 22q11 locus and susceptibility to schizophrenia. Proc. Natl Acad. Sci. USA 99, 16859–16864 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Shaw, S. H. et al. A genome-wide search for schizophrenia susceptibility genes. Am. J. Med. Genet. 81, 364–376 (1998).

    Article  CAS  PubMed  Google Scholar 

  160. Willi, R., Aloy, E. M., Yee, B. K., Feldon, J. & Schwab, M. E. Behavioral characterization of mice lacking the neurite outgrowth inhibitor Nogo-A. Genes Brain Behav. 8, 181–192 (2009).

    Article  CAS  PubMed  Google Scholar 

  161. Braff, D. L., Geyer, M. A. & Swerdlow, N. R. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology 156, 234–258 (2001).

    Article  CAS  PubMed  Google Scholar 

  162. Baruch, I., Hemsley, D. R. & Gray, J. A. Differential performance of acute and chronic schizophrenics in a latent inhibition task. J. Nerv. Ment. Dis. 176, 598–606 (1988).

    Article  CAS  PubMed  Google Scholar 

  163. Baptiste, D. C., Tighe, A. & Fehlings, M. G. Spinal cord injury and neural repair: focus on neuroregenerative approaches for spinal cord injury. Expert Opin. Investig. Drugs 18, 663–673 (2009).

    Article  CAS  PubMed  Google Scholar 

  164. Li, S. et al. Blockade of Nogo-66, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein by soluble nogo-66 receptor promotes axonal sprouting and recovery after spinal cord. J. Neurosci. 24, 10511–10520 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Lee, J. K. et al. Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice. Neuron 66, 663–670 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Kim, J. E., Li, S., GrandPre, T., Qiu, D. & Strittmatter, S. M. Axon regeneration in young adult mice lacking Nogo-A/B. Neuron 38, 187–199 (2003).

    Article  CAS  PubMed  Google Scholar 

  167. Zheng, B. et al. Lack of enhanced spinal regeneration in Nogo-deficient mice. Neuron 38, 213–224 (2003).

    Article  CAS  PubMed  Google Scholar 

  168. Cafferty, W. B., Duffy, P., Huebner, E. & Strittmatter, S. M. MAG and OMgp synergize with Nogo-A to restrict axonal growth and neurological recovery after spinal cord trauma. J. Neurosci. 30, 6825–6837 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Dimou, L. et al. Nogo-A-deficient mice reveal strain-dependent differences in axonal regeneration. J. Neurosci. 26, 5591–5603 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Cafferty, W. B. & Strittmatter, S. M. The Nogo–Nogo receptor pathway limits a spectrum of adult CNS axonal growth. J. Neurosci. 26, 12242–12250 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Kempf, A., Montani, L., Petrinovic, M., Patrignani, A., Dimou, L., Schwab, M. E. EphrinA3 and ephrinB2 act as novel myelin-based neurite outgrowth inhibitors. Soc. Neurosci. Abstr. 411.9 (Chicago, IL, 17–21 October 2009).

  172. Barbaric, I., Miller, G. & Dear, T. N. Appearances can be deceiving: phenotypes of knockout mice. Brief Funct. Genomic Proteomic 6, 91–103 (2007).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The author thanks his laboratory colleagues; in particular A. Buchli, A. Joset, V. Pernet, B. Tews and R. Willi for critically reading the manuscripts. The author's work is supported by grants from the Swiss National Science Foundation (3100AO-122,527/1), the National Center for Competence in Research 'Neural Plasticity & Repair' of the Swiss National Science Foundation, the Spinal Cord Consortium of the Christopher and Dana Reeve Foundation, several EU Framework 7 projects, and the International Foundation of Research in Paraplegia.

Author information

Authors and Affiliations

Authors

Ethics declarations

Competing interests

The author declares no competing financial interests.

Related links

Related links

DATABASES

ClinicalTrials.gov

NCT00406016

FURTHER INFORMATION

Martin E. Schwab's homepage

Glossary

Compartmentalized cultures

Neurons are grown in the middle chamber of a three-chamber culture system. Their neurites are guided into the side chambers under a Teflon ring divider or through microfluidic channels. Neurites can be treated with substances and subsequently analysed separately from the cell bodies.

Tangential migration

A mode of neuron migration that is non-radial. Most interneurons immigrate tangentially into the forebrain cortex from a proliferation zone in the basal ganglia region.

Cortical plate

The upper part of the developing cerebral cortex, where neurons end their migration and start to assemble into the distinct neuronal layers that will form the future adult cortex.

Subplate

A transient layer of cells in the fetal brain that lies beneath the cortical plate.

Intermediate zone

A transient layer in the developing cortex through which neurons migrate on their way from the proliferative zone to the cortical plate. With maturation, this zone is replaced by the subcortical white matter.

Morpholinos

Antisense oligonucleotides that block gene expression.

Tubular ER

A major part of the endoplasmic reticulum (ER) of cells that is characterized by a tubular shape, as opposed to the flat ER cisterns that compose the nuclear membrane, or the Nissl bodies in synthetically highly active neurons.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schwab, M. Functions of Nogo proteins and their receptors in the nervous system. Nat Rev Neurosci 11, 799–811 (2010). https://doi.org/10.1038/nrn2936

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn2936

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing