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Optic Nerve Regeneration

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Neuroprotection and Neuroregeneration for Retinal Diseases

Abstract

In the adult central nervous system (CNS), axon regeneration of damaged neurons is very difficult as the intrinsic regeneration capacity of neurons is suppressed by environmental conditions after birth. Like other mammalian CNS neurons, retinal ganglion cells (RGCs) are unable to regenerate after optic nerve injury and thus, once they are damaged it can cause irreversible visual loss. There are a number of reasons for the failure of axon regeneration. One such reason is the presence of myelin-associated axon growth inhibitors such as Nogo, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp). These molecules create an environment that restricts axon regeneration. On the other hand, there are molecules that promote axon regeneration, such as trophic factors and inflammation-related factors. Recent studies revealed that CNS neurons, including RGCs, can regenerate if the environment surrounding the damaged neurons is suitable for regrowth. This condition may be achieved by application of mixed trophic factors and proinflammatory molecules that promote axon regeneration and/or by suppression of axon growth-inhibition signaling, such as RhoA/ROCK signaling. In this review, recent discoveries on molecular mechanisms underlying optic nerve regeneration are discussed.

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References

  1. Chen MS, Huber AB, van der Haar ME et al (2000) Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 403:434–439

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Wang KC, Koprivica V, Kim JA et al (2002) Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature 417:941–944

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  6. Fournier AE, GrandPre T, Strittmatter SM (2001) Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 409:341–346

    Article  CAS  PubMed  Google Scholar 

  7. Oertle T, Schwab ME (2003) Nogo and its paRTNers. Trends Cell Biol 13:187–194

    Article  CAS  PubMed  Google Scholar 

  8. Lai C, Watson JB, Bloom FE et al (1987) Neural protein 1B236/myelin-associated glycoprotein (MAG) defines a subgroup of the immunoglobulin superfamily. Immunol Rev 100:129–151

    Article  CAS  PubMed  Google Scholar 

  9. Bartsch U, Bandtlow CE, Schnell L et al (1995) Lack of evidence that myelin-associated glycoprotein is a major inhibitor of axonal regeneration in the CNS. Neuron 15:1375–1381

    Article  CAS  PubMed  Google Scholar 

  10. Johnson PW, Abramow-Newerly W, Seilheimer B et al (1989) Recombinant myelin-associated glycoprotein confers neural adhesion and neurite outgrowth function. Neuron 3:377–385

    Article  CAS  PubMed  Google Scholar 

  11. DeBellard ME, Tang S, Mukhopadhyay G et al (1996) Myelin-associated glycoprotein inhibits axonal regeneration from a variety of neurons via interaction with a sialoglycoprotein. Mol Cell Neurosci 7:89–101

    Article  CAS  PubMed  Google Scholar 

  12. Mikol DD, Stefansson K (1988) A phosphatidylinositol-linked peanut agglutinin-binding glycoprotein in central nervous system myelin and on oligodendrocytes. J Cell Biol 106:1273–1279

    Article  CAS  PubMed  Google Scholar 

  13. Habib AA, Marton LS, Allwardt B et al (1998) Expression of the oligodendrocyte-myelin glycoprotein by neurons in the mouse central nervous system. J Neurochem 70:1704–1711

    Article  CAS  PubMed  Google Scholar 

  14. Lee JK, Case LC, Chan AF et al (2009) Generation of an OMgp allelic series in mice. Genesis 47:751–756

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Ji B, Case LC, Liu K et al (2008) Assessment of functional recovery and axonal sprouting in oligodendrocyte-myelin glycoprotein (OMgp) null mice after spinal cord injury. Mol Cell Neurosci 39:258–267

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Domeniconi M, Cao Z, Spencer T et al (2002) Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron 35:283–290

    Article  CAS  PubMed  Google Scholar 

  17. Liu BP, Fournier A, GrandPre T et al (2002) Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor. Science 297:1190–1193

    Article  CAS  PubMed  Google Scholar 

  18. Wang KC, Kim JA, Sivasankaran R et al (2002) P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature 420:74–78

    Article  CAS  PubMed  Google Scholar 

  19. Zheng B, Atwal J, Ho C et al (2005) Genetic deletion of the Nogo receptor does not reduce neurite inhibition in vitro or promote corticospinal tract regeneration in vivo. Proc Natl Acad Sci U S A 102:1205–1210

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Dickendesher TL, Baldwin KT, Mironova YA et al (2012) NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. Nat Neurosci 15:703–712

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. David S, Fry EJ, Lopez-Vales R (2008) Novel roles for Nogo receptor in inflammation and disease. Trends Neurosci 31:221–226

    Article  CAS  PubMed  Google Scholar 

  22. Fry EJ, Ho C, David S (2007) A role for Nogo receptor in macrophage clearance from injured peripheral nerve. Neuron 53:649–662

    Article  CAS  PubMed  Google Scholar 

  23. 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 

  24. Park JB, Yiu G, Kaneko S et al (2005) A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors. Neuron 45:345–351

    Article  CAS  PubMed  Google Scholar 

  25. Shao Z, Browning JL, Lee X et al (2005) TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration. Neuron 45:353–359

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  27. Cai D, Shen Y, De Bellard M et al (1999) Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism. Neuron 22:89–101

    Article  CAS  PubMed  Google Scholar 

  28. Hall A, Lalli G (2010) Rho and Ras GTPases in axon growth, guidance, and branching. Cold Spring Harb Perspect Biol 2:a001818

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  29. Lehmann M, Fournier A, Selles-Navarro I et al (1999) Inactivation of Rho signaling pathway promotes CNS axon regeneration. J Neurosci 19:7537–7547

    CAS  PubMed  Google Scholar 

  30. Bertrand J, Winton MJ, Rodriguez-Hernandez N et al (2005) Application of Rho antagonist to neuronal cell bodies promotes neurite growth in compartmented cultures and regeneration of retinal ganglion cell axons in the optic nerve of adult rats. J Neurosci 25:1113–1121

    Article  CAS  PubMed  Google Scholar 

  31. Fischer D, Petkova V, Thanos S et al (2004) Switching mature retinal ganglion cells to a robust growth state in vivo: gene expression and synergy with RhoA inactivation. J Neurosci 24:8726–8740

    Article  CAS  PubMed  Google Scholar 

  32. Lingor P, Teusch N, Schwarz K et al (2007) Inhibition of Rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo. J Neurochem 103:181–189

    CAS  PubMed  Google Scholar 

  33. Lingor P, Tonges L, Pieper N et al (2008) ROCK inhibition and CNTF interact on intrinsic signalling pathways and differentially regulate survival and regeneration in retinal ganglion cells. Brain 131:250–263

    PubMed  Google Scholar 

  34. Ahmed Z, Berry M, Logan A (2009) ROCK inhibition promotes adult retinal ganglion cell neurite outgrowth only in the presence of growth promoting factors. Mol Cell Neurosci 42:128–133

    Article  CAS  PubMed  Google Scholar 

  35. Marino S, Krimpenfort P, Leung C et al (2002) PTEN is essential for cell migration but not for fate determination and tumourigenesis in the cerebellum. Development 129:3513–3522

    CAS  PubMed  Google Scholar 

  36. Cantrup R, Dixit R, Palmesino E et al (2012) Cell-type specific roles for PTEN in establishing a functional retinal architecture. PLoS One 7:e32795

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Drinjakovic J, Jung H, Campbell DS et al (2010) E3 ligase Nedd4 promotes axon branching by downregulating PTEN. Neuron 65:341–357

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Park KK, Liu K, Hu Y et al (2008) Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 322:963–966

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Sun F, Park KK, Belin S et al (2011) Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature 480:372–375

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Ebadi M, Bashir RM, Heidrick ML et al (1997) Neurotrophins and their receptors in nerve injury and repair. Neurochem Int 30:347–374

    Article  CAS  PubMed  Google Scholar 

  41. LaVail MM, Unoki K, Yasumura D et al (1992) Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light. Proc Natl Acad Sci U S A 89:11249–11253

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Harada T, Harada C, Kohsaka S et al (2002) Microglia-Müller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration. J Neurosci 22:9228–9236

    CAS  PubMed  Google Scholar 

  43. Harada C, Harada T, Quah HM et al (2005) Role of neurotrophin-4/5 in neural cell death during retinal development and ischemic retinal injury in vivo. Invest Ophthalmol Vis Sci 46:669–673

    Article  PubMed  Google Scholar 

  44. Harada C, Guo X, Namekata K et al (2011) Glia- and neuron-specific functions of TrkB signalling during retinal degeneration and regeneration. Nat Commun 2:189

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  45. Parada LF, Tsoulfas P, Tessarollo L et al (1992) The Trk family of tyrosine kinases: receptors for NGF-related neurotrophins. Cold Spring Harb Symp Quant Biol 57:43–51

    Article  CAS  PubMed  Google Scholar 

  46. Greene LA, Kaplan DR (1995) Early events in neurotrophin signalling via Trk and p75 receptors. Curr Opin Neurobiol 5:579–587

    Article  CAS  PubMed  Google Scholar 

  47. Harada T, Harada C, Nakayama N et al (2000) Modification of glial-neuronal cell interactions prevents photoreceptor apoptosis during light-induced retinal degeneration. Neuron 26:533–541

    Article  CAS  PubMed  Google Scholar 

  48. Bredesen DE, Rabizadeh S (1997) p75NTR and apoptosis: Trk-dependent and Trk-independent effects. Trends Neurosci 20:287–290

    Article  CAS  PubMed  Google Scholar 

  49. Nakamura K, Namekata K, Harada C et al (2007) Intracellular sortilin expression pattern regulates proNGF-induced naturally occurring cell death during development. Cell Death Differ 14:1552–1554

    Article  CAS  PubMed  Google Scholar 

  50. Harada C, Harada T, Nakamura K et al (2006) Effect of p75NTR on the regulation of naturally occurring cell death and retinal ganglion cell number in the mouse eye. Dev Biol 290:57–65

    Article  CAS  PubMed  Google Scholar 

  51. Harada T, Harada C, Parada LF (2007) Molecular regulation of visual system development: more than meets the eye. Genes Dev 21:367–378

    Article  CAS  PubMed  Google Scholar 

  52. Mey J, Thanos S (1993) Intravitreal injections of neurotrophic factors support the survival of axotomized retinal ganglion cells in adult rats in vivo. Brain Res 602:304–317

    Article  CAS  PubMed  Google Scholar 

  53. Cohen A, Bray GM, Aguayo AJ (1994) Neurotrophin-4/5 (NT-4/5) increases adult rat retinal ganglion cell survival and neurite outgrowth in vitro. J Neurobiol 25:953–959

    Article  CAS  PubMed  Google Scholar 

  54. Mansour-Robaey S, Clarke DB, Wang YC et al (1994) Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells. Proc Natl Acad Sci U S A 91:1632–1636

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Pernet V, Di Polo A (2006) Synergistic action of brain-derived neurotrophic factor and lens injury promotes retinal ganglion cell survival, but leads to optic nerve dystrophy in vivo. Brain 129:1014–1026

    Article  PubMed  Google Scholar 

  56. Sievers J, Hausmann B, Unsicker K et al (1987) Fibroblast growth factors promote the survival of adult rat retinal ganglion cells after transection of the optic nerve. Neurosci Lett 76:157–162

    Article  CAS  PubMed  Google Scholar 

  57. Koeberle PD, Ball AK (1998) Effects of GDNF on retinal ganglion cell survival following axotomy. Vision Res 38:1505–1515

    Article  CAS  PubMed  Google Scholar 

  58. Koeberle PD, Ball AK (2002) Neurturin enhances the survival of axotomized retinal ganglion cells in vivo: combined effects with glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor. Neuroscience 110:555–567

    Article  CAS  PubMed  Google Scholar 

  59. Yin Y, Cui Q, Li Y et al (2003) Macrophage-derived factors stimulate optic nerve regeneration. J Neurosci 23:2284–2293

    CAS  PubMed  Google Scholar 

  60. Correale J, Villa A (2004) The neuroprotective role of inflammation in nervous system injuries. J Neurol 251:1304–1316

    Article  PubMed  Google Scholar 

  61. Butovsky O, Ziv Y, Schwartz A et al (2006) Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol Cell Neurosci 31:149–160

    Article  CAS  PubMed  Google Scholar 

  62. Leroy K, Yilmaz Z, Brion JP (2007) Increased level of active GSK-3beta in Alzheimer’s disease and accumulation in argyrophilic grains and in neurones at different stages of neurofibrillary degeneration. Neuropathol Appl Neurobiol 33:43–55

    Article  CAS  PubMed  Google Scholar 

  63. Lorber B, Berry M, Logan A (2005) Lens injury stimulates adult mouse retinal ganglion cell axon regeneration via both macrophage- and lens-derived factors. Eur J Neurosci 21:2029–2034

    Article  PubMed  Google Scholar 

  64. Fischer D, Pavlidis M, Thanos S (2000) Cataractogenic lens injury prevents traumatic ganglion cell death and promotes axonal regeneration both in vivo and in culture. Invest Ophthalmol Vis Sci 41:3943–3954

    CAS  PubMed  Google Scholar 

  65. Leon S, Yin Y, Nguyen J et al (2000) Lens injury stimulates axon regeneration in the mature rat optic nerve. J Neurosci 20:4615–4626

    CAS  PubMed  Google Scholar 

  66. Fischer D, He Z, Benowitz LI (2004) Counteracting the Nogo receptor enhances optic nerve regeneration if retinal ganglion cells are in an active growth state. J Neurosci 24:1646–1651

    Article  CAS  PubMed  Google Scholar 

  67. Lazarov-Spiegler O, Solomon AS, Schwartz M (1998) Peripheral nerve-stimulated macrophages simulate a peripheral nerve-like regenerative response in rat transected optic nerve. Glia 24:329–337

    Article  CAS  PubMed  Google Scholar 

  68. Lazarov-Spiegler O, Solomon AS, Zeev-Brann AB et al (1996) Transplantation of activated macrophages overcomes central nervous system regrowth failure. FASEB J 10:1296–1302

    CAS  PubMed  Google Scholar 

  69. Rapalino O, Lazarov-Spiegler O, Agranov E et al (1998) Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med 4:814–821

    Article  CAS  PubMed  Google Scholar 

  70. Berry MJ 2nd, Brivanlou IH, Jordan TA et al (1999) Anticipation of moving stimuli by the retina. Nature 398:334–338

    Article  CAS  PubMed  Google Scholar 

  71. Berry M, Carlile J, Hunter A (1996) Peripheral nerve explants grafted into the vitreous body of the eye promote the regeneration of retinal ganglion cell axons severed in the optic nerve. J Neurocytol 25:147–170

    Article  CAS  PubMed  Google Scholar 

  72. Okada T, Ichikawa M, Tokita Y et al (2005) Intravitreal macrophage activation enables cat retinal ganglion cells to regenerate injured axons into the mature optic nerve. Exp Neurol 196:153–163

    Article  PubMed  Google Scholar 

  73. Yin Y, Henzl MT, Lorber B et al (2006) Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nat Neurosci 9:843–852

    Article  CAS  PubMed  Google Scholar 

  74. Yin Y, Cui Q, Gilbert HY et al (2009) Oncomodulin links inflammation to optic nerve regeneration. Proc Natl Acad Sci U S A 106:19587–19592

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  75. Kurimoto T, Yin Y, Habboub G et al (2013) Neutrophils express oncomodulin and promote optic nerve regeneration. J Neurosci 33:14816–14824

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. de Lima S, Koriyama Y, Kurimoto T et al (2012) Full-length axon regeneration in the adult mouse optic nerve and partial recovery of simple visual behaviors. Proc Natl Acad Sci U S A 109:9149–9154

    Article  PubMed Central  PubMed  Google Scholar 

  77. Hirai S, de Cui F, Miyata T et al (2006) The c-Jun N-terminal kinase activator dual leucine zipper kinase regulates axon growth and neuronal migration in the developing cerebral cortex. J Neurosci 26:11992–12002

    Article  CAS  PubMed  Google Scholar 

  78. Ghosh AS, Wang B, Pozniak CD et al (2011) DLK induces developmental neuronal degeneration via selective regulation of proapoptotic JNK activity. J Cell Biol 194:751–764

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Itoh A, Horiuchi M, Wakayama K et al (2011) ZPK/DLK, a mitogen-activated protein kinase kinase kinase, is a critical mediator of programmed cell death of motoneurons. J Neurosci 31:7223–7228

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Watkins TA, Wang B, Huntwork-Rodriguez S et al (2013) DLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury. Proc Natl Acad Sci U S A 110:4039–4044

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  81. Hammarlund M, Nix P, Hauth L et al (2009) Axon regeneration requires a conserved MAP kinase pathway. Science 323:802–806

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Yan D, Wu Z, Chisholm AD et al (2009) The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration. Cell 138:1005–1018

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  83. Xiong X, Wang X, Ewanek R et al (2010) Protein turnover of the Wallenda/DLK kinase regulates a retrograde response to axonal injury. J Cell Biol 191:211–223

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Shin JE, Cho Y, Beirowski B et al (2012) Dual leucine zipper kinase is required for retrograde injury signaling and axonal regeneration. Neuron 74:1015–1022

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Matsuzawa A, Saegusa K, Noguchi T et al (2005) ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity. Nat Immunol 6:587–592

    Article  CAS  PubMed  Google Scholar 

  86. Katome T, Namekata K, Guo X et al (2013) Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve injury. Cell Death Differ 20:270–280

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Kikuchi M, Tenneti L, Lipton SA (2000) Role of p38 mitogen-activated protein kinase in axotomy-induced apoptosis of rat retinal ganglion cells. J Neurosci 20:5037–5044

    CAS  PubMed  Google Scholar 

  88. Harada C, Nakamura K, Namekata K et al (2006) Role of apoptosis signal-regulating kinase 1 in stress-induced neural cell apoptosis in vivo. Am J Pathol 168:261–269

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  89. Harada C, Namekata K, Guo X et al (2010) ASK1 deficiency attenuates neural cell death in GLAST-deficient mice, a model of normal tension glaucoma. Cell Death Differ 17:1751–1759

    Article  CAS  PubMed  Google Scholar 

  90. Guo X, Harada C, Namekata K et al (2010) Regulation of the severity of neuroinflammation and demyelination by TLR-ASK1-p38 pathway. EMBO Mol Med 2:504–515

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  91. Namekata K, Enokido Y, Iwasawa K et al (2004) MOCA induces membrane spreading by activating Rac1. J Biol Chem 279:14331–14337

    Article  CAS  PubMed  Google Scholar 

  92. Namekata K, Harada C, Taya C et al (2010) Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex. Proc Natl Acad Sci U S A 107:7586–7591

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  93. Namekata K, Watanabe H, Guo X et al (2012) Dock3 regulates BDNF-TrkB signaling for neurite outgrowth by forming a ternary complex with Elmo and RhoG. Genes Cells 17:688–697

    Article  CAS  PubMed  Google Scholar 

  94. Namekata K, Harada C, Guo X et al (2012) Dock3 stimulates axonal outgrowth via GSK-3beta-mediated microtubule assembly. J Neurosci 32:264–274

    Article  CAS  PubMed  Google Scholar 

  95. Yoshimura T, Kawano Y, Arimura N et al (2005) GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity. Cell 120:137–149

    Article  CAS  PubMed  Google Scholar 

  96. Kim WY, Zhou FQ, Zhou J et al (2006) Essential roles for GSK-3s and GSK-3-primed substrates in neurotrophin-induced and hippocampal axon growth. Neuron 52:981–996

    Article  CAS  PubMed  Google Scholar 

  97. Kumar P, Lyle KS, Gierke S et al (2009) GSK3beta phosphorylation modulates CLASP-microtubule association and lamella microtubule attachment. J Cell Biol 184:895–908

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  98. Chen Q, Peto CA, Shelton GD et al (2009) Loss of modifier of cell adhesion reveals a pathway leading to axonal degeneration. J Neurosci 29:118–130

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  99. Kashiwa A, Yoshida H, Lee S et al (2000) Isolation and characterization of novel presenilin binding protein. J Neurochem 75:109–116

    Article  CAS  PubMed  Google Scholar 

  100. Chen Q, Kimura H, Schubert D (2002) A novel mechanism for the regulation of amyloid precursor protein metabolism. J Cell Biol 158:79–89

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  101. Chen Q, Yoshida H, Schubert D et al (2001) Presenilin binding protein is associated with neurofibrillary alterations in Alzheimer’s disease and stimulates tau phosphorylation. Am J Pathol 159:1597–1602

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Visual Research Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan

    Kazuhiko Namekata

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  1. Kazuhiko Namekata
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Correspondence to Kazuhiko Namekata .

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  1. Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    Toru Nakazawa

  2. Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan

    Yasushi Kitaoka

  3. Visual Research Project, Tokyo Metropolitan Inst of Med Sci, Tokyo, Japan

    Takayuki Harada

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Namekata, K. (2014). Optic Nerve Regeneration. In: Nakazawa, T., Kitaoka, Y., Harada, T. (eds) Neuroprotection and Neuroregeneration for Retinal Diseases. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54965-9_23

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