Skip to main content

Advertisement

SpringerLink
Log in

Axonal regeneration inhibitors: emerging therapeutic options

  • Review Article
  • Published:
Acta Neurologica Belgica Aims and scope Submit manuscript

Abstract

For the most part, the central nervous system is unable to regenerate. The majority of injuries of vascular, inflammatory, degenerative and traumatic aetiology lead to an irreversible loss of central nervous system function. The paper presents the role of Nogo-A, MAG and OMgp proteins in the inhibition of central nervous system regeneration, and their potential clinical significance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Schwab JM, Failli V, Chetodal A (2005) Injury-related dynamic myelin/oligodendrocyte axon-outgrowth inhibition in the central nervous system. Lancet 365:2055–2057

    Article  CAS  PubMed  Google Scholar 

  2. Tello Y (1911) La influencia del neurotropismo en la regeneracion de los centros nerviosos. Trab Lab Invest Biol 9:123–159

    Google Scholar 

  3. Berry M (1982) Post-injury myelin-breakdown products inhibit axonal growth: an hypothesis to explain the failure of axonal regeneration in the mammalian central nervous system. Bibliotheca Anatomica 23:1–11

    PubMed  Google Scholar 

  4. Silver J, Miller JH (2004) Regeneration beyond the glial scar. Nat Rev Neurosci 5:146–156

    Article  CAS  PubMed  Google Scholar 

  5. Morgenstern DA, Asher RA, Fawcett JW (2002) Chondroitin sulphate proteoglycans in the CNS injury response. Prog Brain Res 137:313–332

    Article  CAS  PubMed  Google Scholar 

  6. Schwab ME, Bartholdi D (1996) Degeneration and regeneration of axons in the lesioned spinal cord. Physiol Rev 76:319–370

    CAS  PubMed  Google Scholar 

  7. Carulli D, Laabs T, Geller HM et al (2005) Chondroitin sulfate proteoglycans in neural development and regeneration. Curr Opin Neurobiol 15(2):252

    Article  CAS  Google Scholar 

  8. Yamashita T, Higuchi H, Tohyama M (2002) The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho. J Cell Biol 157(4):565–570

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Mi S, Lee X, Shao Z et al (2004) LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci 7:221–228

    Article  CAS  PubMed  Google Scholar 

  10. Yamashita T, Fujitani M, Hata K et al (2005) Rho/Rho-kinase as potential therapeutic target for CNS injury. Gene Ther Mol Biol 9:265–268

    Google Scholar 

  11. Caroni P, Schwab ME (1988) Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron 1:85–96

    Article  CAS  PubMed  Google Scholar 

  12. Grandpré T, Nakamura F, Vartanian T et al (2000) Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature 403(6768):439–444

    Article  PubMed  Google Scholar 

  13. Huber AB, Weinmann O, Brösamle C et al (2002) Patterns of Nogo mRNA and protein expression in the developing and adult rat and after CNS lesions. J Neurosci 22(9):3553–3567

    CAS  PubMed  Google Scholar 

  14. Prinjha RK, McAdam RA, Burbridge SA et al (2004) Strategies for developing Nogo antagonists. J Drug Discov Today Ther Strateg 9:21–27

    Article  Google Scholar 

  15. Prinjha R, Moore SE, Vinson M et al (2000) Inhibitor of neurite outhgrowth in humans. Nature 403:383–384

    Article  CAS  PubMed  Google Scholar 

  16. Oertle T, Klinger M, Stuermer CAO et al (2003) A reticular rhapsody: phylogenic evolution and nomenclature of the RTN/Nogo gene family. FASEB J 17(10):1238–1247

    Article  CAS  PubMed  Google Scholar 

  17. McKerraccher L, David S, Jackson DL et al (1994) Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor on neurite growth. Neuron 13(4):805–811

    Article  Google Scholar 

  18. Cad D, Qiu J, Cao Z et al (2001) Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate. J Neurosci 21(13):4731–4739

    Google Scholar 

  19. Huang JK, Phillips GR, Roth AD et al (2005) Glial membranes at the node of Ranvier prevent neurite outgrowth. Science 310:1813–1817

    Article  CAS  PubMed  Google Scholar 

  20. Atwak JK, Pinknston-Gosse J, Syken J et al (2008) PirB is a functional receptor for myelin inhibitors of axonal regeneration. Science 322:967–970

    Article  Google Scholar 

  21. Wong ST, Henley JR, Kanning KC et al (2003) A p75 (NTR) and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein. Nat Neurosci 5(12):1302–1308

    Article  Google Scholar 

  22. Fournier AE et al (2001) Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 18(409):341–346

    Article  Google Scholar 

  23. Grandpré T, Li S, Strittmatter SM (2002) Nogo-66 receptor antagonist peptide promotes axonal regeneration. Nature 417(6888):547–551

    Article  PubMed  Google Scholar 

  24. Li S, Strittmatter SM (2003) Delayed systemic Nogo-66 receptor antagonist promotes recovery from spinal cord injury. J Neurosci 23(10):4219–4227

    CAS  PubMed  Google Scholar 

  25. Nowak JM, Grzanka A, Żuryń A et al (2008) Rodzina białek Rho i ich rola w cytoszkielecie komórki. Postepy Hig Med Dosw 62:110–117

    Google Scholar 

  26. Saski T, Takai Y (1998) The Rho small G protein family-Rho GDI system as a temporal and spatial determinant for cytoskeletal control. Biochem Biophys Res Commun 245:641–645

    Article  Google Scholar 

  27. Dergham P, Ellezam B, Essagian CH et al (2002) Rho signaling pathway targeted to promote spinal cord repair. J Neurosci 22(15):6570–6577

    CAS  PubMed  Google Scholar 

  28. Fournier A, Takizawa B, Strittmatter SM et al (2003) Rho kinase inhibition enhances axonal regeneration in the injured CNS. J Neuosci 23(4):1416–1423

    CAS  Google Scholar 

  29. Yamashita T, Tohyama M (2003) The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI. Nat Neuosci 6L:461–467

    Google Scholar 

  30. He Z, Koprivica V (2004) The Nogo signaling pathway for regeneration block. Annu Rev Neuosci 27:341–368

    Article  CAS  Google Scholar 

  31. Bandtlow CE, Schmidt MF, Hassinger TD et al (1993) Role of intracellular calcium in NI-35-evoked collapse of neuronal growth cones. Science 259:80–83

    Article  CAS  PubMed  Google Scholar 

  32. Nógrádi A, Szabó A, Pintér S et al (2007) Delayed riluzole treatment is able to rescue injured rat spinal motoneurons. Neuroscience 144:431–438

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study received no financial support.

Conflict of interest

The authors report no financial or other conflict of interest associated with this study.

Author information

Authors and Affiliations

  1. Nicolaus Copernicus University, Toruń, Poland

    T. W. Rosochowicz, S. Wrotek & W. Kozak

Authors
  1. T. W. Rosochowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Wrotek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Kozak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. W. Rosochowicz.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rosochowicz, T.W., Wrotek, S. & Kozak, W. Axonal regeneration inhibitors: emerging therapeutic options. Acta Neurol Belg 115, 527–532 (2015). https://doi.org/10.1007/s13760-015-0425-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13760-015-0425-0

Keywords

Search

Navigation