Glial Inhibition of CNS Axon Regeneration

Overview

Journal Nat Rev Neurosci

Specialty Neurology

Date 2006 Jul 22

PMID 16858390

Citations 688

Authors

Glenn Yiu

Zhigang He

Affiliations

Soon will be listed here.

Abstract

Damage to the adult CNS often leads to persistent deficits due to the inability of mature axons to regenerate after injury. Mounting evidence suggests that the glial environment of the adult CNS, which includes inhibitory molecules in CNS myelin as well as proteoglycans associated with astroglial scarring, might present a major hurdle for successful axon regeneration. Here, we evaluate the molecular basis of these inhibitory influences and their contributions to the limitation of long-distance axon repair and other types of structural plasticity. Greater insight into glial inhibition is crucial for developing therapies to promote functional recovery after neural injury.

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References

Venkatesh K, Chivatakarn O, Lee H, Joshi P, Kantor D, Newman B . The Nogo-66 receptor homolog NgR2 is a sialic acid-dependent receptor selective for myelin-associated glycoprotein. J Neurosci. 2005; 25(4):808-22. PMC: 6725623. DOI: 10.1523/JNEUROSCI.4464-04.2005. View

He Z, Koprivica V . The Nogo signaling pathway for regeneration block. Annu Rev Neurosci. 2004; 27:341-68. DOI: 10.1146/annurev.neuro.27.070203.144340. View

Lee J, Kim J, Sivula M, Strittmatter S . Nogo receptor antagonism promotes stroke recovery by enhancing axonal plasticity. J Neurosci. 2004; 24(27):6209-17. PMC: 6729662. DOI: 10.1523/JNEUROSCI.1643-04.2004. View

Tom V, Steinmetz M, Miller J, Doller C, Silver J . Studies on the development and behavior of the dystrophic growth cone, the hallmark of regeneration failure, in an in vitro model of the glial scar and after spinal cord injury. J Neurosci. 2004; 24(29):6531-9. PMC: 6729861. DOI: 10.1523/JNEUROSCI.0994-04.2004. View

Hasegawa Y, Fujitani M, Hata K, Tohyama M, Yamagishi S, Yamashita T . Promotion of axon regeneration by myelin-associated glycoprotein and Nogo through divergent signals downstream of Gi/G. J Neurosci. 2004; 24(30):6826-32. PMC: 6729720. DOI: 10.1523/JNEUROSCI.1856-04.2004. View

Kim J, Liu B, Park J, Strittmatter S . Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury. Neuron. 2004; 44(3):439-51. DOI: 10.1016/j.neuron.2004.10.015. View

David S, Aguayo A . Axonal elongation into peripheral nervous system "bridges" after central nervous system injury in adult rats. Science. 1981; 214(4523):931-3. DOI: 10.1126/science.6171034. View

Schwab M, Thoenen H . Dissociated neurons regenerate into sciatic but not optic nerve explants in culture irrespective of neurotrophic factors. J Neurosci. 1985; 5(9):2415-23. PMC: 6565336. View

Cole G, LOEWY A, Glaser L . Neuronal cell-cell adhesion depends on interactions of N-CAM with heparin-like molecules. Nature. 1986; 320(6061):445-7. DOI: 10.1038/320445a0. View

10.

Salzer J, Holmes W, Colman D . The amino acid sequences of the myelin-associated glycoproteins: homology to the immunoglobulin gene superfamily. J Cell Biol. 1987; 104(4):957-65. PMC: 2114452. DOI: 10.1083/jcb.104.4.957. View

11.

Lai C, Watson J, Bloom F, Sutcliffe J, Milner R . Neural protein 1B236/myelin-associated glycoprotein (MAG) defines a subgroup of the immunoglobulin superfamily. Immunol Rev. 1987; 100:129-51. DOI: 10.1111/j.1600-065x.1987.tb00530.x. View

12.

Muller C, Best J . Ocular dominance plasticity in adult cat visual cortex after transplantation of cultured astrocytes. Nature. 1989; 342(6248):427-30. DOI: 10.1038/342427a0. View

13.

Mikol D, Gulcher J, Stefansson K . The oligodendrocyte-myelin glycoprotein belongs to a distinct family of proteins and contains the HNK-1 carbohydrate. J Cell Biol. 1990; 110(2):471-9. PMC: 2116011. DOI: 10.1083/jcb.110.2.471. View

14.

Huang J, Phillips G, Roth A, Pedraza L, Shan W, Belkaid W . Glial membranes at the node of Ranvier prevent neurite outgrowth. Science. 2005; 310(5755):1813-7. DOI: 10.1126/science.1118313. View

15.

Hsieh S, Ferraro G, Fournier A . Myelin-associated inhibitors regulate cofilin phosphorylation and neuronal inhibition through LIM kinase and Slingshot phosphatase. J Neurosci. 2006; 26(3):1006-15. PMC: 6675360. DOI: 10.1523/JNEUROSCI.2806-05.2006. View

16.

Voeltz G, Prinz W, Shibata Y, Rist J, Rapoport T . A class of membrane proteins shaping the tubular endoplasmic reticulum. Cell. 2006; 124(3):573-86. DOI: 10.1016/j.cell.2005.11.047. View

17.

Papadopoulos C, Tsai S, Cheatwood J, Bollnow M, Kolb B, Schwab M . Dendritic plasticity in the adult rat following middle cerebral artery occlusion and Nogo-a neutralization. Cereb Cortex. 2005; 16(4):529-36. DOI: 10.1093/cercor/bhi132. View

18.

Trajkovic K, Dhaunchak A, Goncalves J, Wenzel D, Schneider A, Bunt G . Neuron to glia signaling triggers myelin membrane exocytosis from endosomal storage sites. J Cell Biol. 2006; 172(6):937-48. PMC: 2063736. DOI: 10.1083/jcb.200509022. View

19.

Yang Z, Suzuki R, Daniels S, Brunquell C, Sala C, Nishiyama A . NG2 glial cells provide a favorable substrate for growing axons. J Neurosci. 2006; 26(14):3829-39. PMC: 6674118. DOI: 10.1523/JNEUROSCI.4247-05.2006. View

20.

Massey J, Hubscher C, Wagoner M, Decker J, Amps J, Silver J . Chondroitinase ABC digestion of the perineuronal net promotes functional collateral sprouting in the cuneate nucleus after cervical spinal cord injury. J Neurosci. 2006; 26(16):4406-14. PMC: 6673998. DOI: 10.1523/JNEUROSCI.5467-05.2006. View