MAG, Myelin and Overcoming Growth Inhibition in the CNS

Overview

Journal Front Mol Neurosci

Specialty Molecular Biology

Date 2015 Oct 7

PMID 26441514

Citations 36

Authors

Lisa McKerracher

Kenneth M Rosen

Affiliations

Soon will be listed here.

Abstract

While neurons in the central nervous system (CNS) have the capacity to regenerate their axons after injury, they fail to do so, in part because regeneration is limited by growth inhibitory proteins present in CNS myelin. Myelin-associated glycoprotein (MAG) was the first myelin-derived growth inhibitory protein identified, and its inhibitory activity was initially elucidated in 1994 independently by the Filbin lab and the McKerracher lab using cell-based and biochemical techniques, respectively. Since that time we have gained a wealth of knowledge concerning the numerous growth inhibitory proteins that are present in myelin, and we also have dissected many of the neuronal signaling pathways that act as stop signs for axon regeneration. Here we give an overview of the early research efforts that led to the identification of myelin-derived growth inhibitory proteins, and the importance of this family of proteins for understanding neurotrauma and CNS diseases. We further provide an update on how this knowledge has been translated towards current clinical studies in regenerative medicine.

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References

Shibata A, Wright M, David S, McKerracher L, Braun P, Kater S . Unique responses of differentiating neuronal growth cones to inhibitory cues presented by oligodendrocytes. J Cell Biol. 1998; 142(1):191-202. PMC: 2133022. DOI: 10.1083/jcb.142.1.191. View

Tang S, Woodhall R, Shen Y, DeBellard M, Saffell J, Doherty P . Soluble myelin-associated glycoprotein (MAG) found in vivo inhibits axonal regeneration. Mol Cell Neurosci. 1997; 9(5-6):333-46. DOI: 10.1006/mcne.1997.0633. View

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

Lee J, Geoffroy C, Chan A, Tolentino K, Crawford M, Leal M . Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice. Neuron. 2010; 66(5):663-70. PMC: 2896331. DOI: 10.1016/j.neuron.2010.05.002. View

Habib A, Marton L, Allwardt B, Gulcher J, Mikol D, Hognason T . Expression of the oligodendrocyte-myelin glycoprotein by neurons in the mouse central nervous system. J Neurochem. 1998; 70(4):1704-11. DOI: 10.1046/j.1471-4159.1998.70041704.x. View

Dubreuil C, Winton M, McKerracher L . Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system. J Cell Biol. 2003; 162(2):233-43. PMC: 2172802. DOI: 10.1083/jcb.200301080. 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

Cai D, Qiu J, Cao Z, McAtee M, Bregman B, Filbin M . Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate. J Neurosci. 2001; 21(13):4731-9. PMC: 6762375. View

Ji B, Case L, Liu K, Shao Z, Lee X, Yang Z . Assessment of functional recovery and axonal sprouting in oligodendrocyte-myelin glycoprotein (OMgp) null mice after spinal cord injury. Mol Cell Neurosci. 2008; 39(2):258-67. PMC: 2646371. DOI: 10.1016/j.mcn.2008.07.004. View

10.

Grandpre T, Nakamura F, Vartanian T, Strittmatter S . Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature. 2000; 403(6768):439-44. DOI: 10.1038/35000226. View

11.

David S, Braun P, Jackson D, Kottis V, McKerracher L . Laminin overrides the inhibitory effects of peripheral nervous system and central nervous system myelin-derived inhibitors of neurite growth. J Neurosci Res. 1995; 42(4):594-602. DOI: 10.1002/jnr.490420417. View

12.

Fournier A, McKerracher L . Tubulin expression and axonal transport in injured and regenerating neurons in the adult mammalian central nervous system. Biochem Cell Biol. 1995; 73(9-10):659-64. DOI: 10.1139/o95-073. View

13.

Oertle T, van der Haar M, Bandtlow C, Robeva A, Burfeind P, Buss A . Nogo-A inhibits neurite outgrowth and cell spreading with three discrete regions. J Neurosci. 2003; 23(13):5393-406. PMC: 6741224. View

14.

Atwal J, Pinkston-Gosse J, Syken J, Stawicki S, Wu Y, Shatz C . PirB is a functional receptor for myelin inhibitors of axonal regeneration. Science. 2008; 322(5903):967-70. DOI: 10.1126/science.1161151. View

15.

Fruttiger M, Montag D, Schachner M, Martini R . Crucial role for the myelin-associated glycoprotein in the maintenance of axon-myelin integrity. Eur J Neurosci. 1995; 7(3):511-5. DOI: 10.1111/j.1460-9568.1995.tb00347.x. View

16.

Schwab M . Functions of Nogo proteins and their receptors in the nervous system. Nat Rev Neurosci. 2010; 11(12):799-811. DOI: 10.1038/nrn2936. View

17.

Turnley A, Bartlett P . MAG and MOG enhance neurite outgrowth of embryonic mouse spinal cord neurons. Neuroreport. 1998; 9(9):1987-90. DOI: 10.1097/00001756-199806220-00013. View

18.

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

19.

Park J, Yiu G, Kaneko S, Wang J, Chang J, He X . A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors. Neuron. 2005; 45(3):345-51. DOI: 10.1016/j.neuron.2004.12.040. View

20.

Filbin . The Muddle with MAG. Mol Cell Neurosci. 1996; 8(2/3):84-92. DOI: 10.1006/mcne.1996.0047. View