Molecular targets for axon regeneration: Focus on the intrinsic pathways

Expert Opinion on Therapeutic Targets

Volumn 13, Issue 12, 2009, Pages 1387-1398

  Giovanni, Simone Di ^a  

^a UNIVERSITY OF TÜBINGEN   (Germany)

Author keywords

axon regeneration; axonal injury; brain injury; neuron intrinsic pathways; plasticity; spinal cord injury; stroke

Indexed keywords

BETA TUBULIN; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; CYTOSKELETON PROTEIN; GALECTIN 1; MAMMALIAN TARGET OF RAPAMYCIN; NEUROMODULIN; NEUROTROPHIN; NEUROTROPHIN 3; ONCOMODULIN; PROTEIN C JUN; PROTEIN P53; ROLIPRAM; SEMAPHORIN; STAT3 PROTEIN; STRESS ACTIVATED PROTEIN KINASE; TRANSCRIPTION FACTOR; MTORC1 PROTEIN, HUMAN; NERVE GROWTH FACTOR;

AXONAL INJURY; CELL DEATH; GENE EXPRESSION; GENE THERAPY; HUMAN; INTRACELLULAR SIGNALING; MOLECULAR DYNAMICS; MOLECULAR INTERACTION; MOLECULARLY TARGETED THERAPY; NERVE FIBER REGENERATION; NERVE SPROUTING; NEUROMODULATION; NONHUMAN; PROTEIN MODIFICATION; PROTEIN SYNTHESIS; REVIEW; SCIATIC NERVE; SPINAL GANGLION; ANIMAL; BIOSYNTHESIS; DRUG EFFECT; NERVE DEGENERATION; NERVE FIBER; NERVE REGENERATION; NERVE TRACT; PATHOLOGY; PHYSIOLOGY;

ANIMALS; AXONS; CYTOSKELETAL PROTEINS; HUMANS; NERVE DEGENERATION; NERVE GROWTH FACTORS; NERVE REGENERATION; NEURAL PATHWAYS; TRANSCRIPTION FACTORS;

EID: 75349109284     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728220903307517     Document Type: Review

References (131)

1. Yakovlev AG, Faden AI. Molecular biology of CNS injury. J Neurotrauma 1995;12(5):767-77
2. Springer JE. Apoptotic cell death following traumatic injury to the central nervous system. J Biochem Mol Biol 2002;35(1):94-105 (Pubitemid 35216585)
3. Lucas SM, Rothwell NJ, Gibson RM. The role of inflammation in CNS injury and disease. Br J Pharmacol 2006;147(Suppl 1):S232-40 (Pubitemid 43077281)
4. Allan SM, Rothwell NJ. Inflammation in central nervous system injury. Philos Trans R Soc Lond B Biol Sci 2003;358(1438):1669-77 (Pubitemid 37298635)
5. Murkin JM. Inflammatory responses and CNS injury: implications, prophylaxis, and treatment. Heart Surg Forum 2003;6(4):193-5 (Pubitemid 37063319)
6. Hayashi T, Noshita N, Sugawara T, Chan PH. Temporal profile of angiogenesis and expression of related genes in the brain after ischemia. J Cereb Blood Flow Metab 2003;23(2):166-80 (Pubitemid 36188455)
7. Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med 2000;6(4):389-95 (Pubitemid 30208155)
8. Arvidsson A, Collin T, Kirik D, et al. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 2002;8(9):963-70 (Pubitemid 35033700)
9. Parent JM, Vexler ZS, Gong C, et al. Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol 2002;52(6):802-13 (Pubitemid 35403191)
10. Thored P, Arvidsson A, Cacci E. et al. Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells 2006;24(3):739-47 (Pubitemid 44464779)
11. Zhang RL, Zhang ZG, Chopp M. Neurogenesis in the adult ischemic brain: generation, migration, survival, and restorative therapy. Neuroscientist 2005;11(5):408-16 (Pubitemid 41339227)
12. Lu P, Jones LL, Snyder EY, Tuszynski MH. Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Exp Neurol 2003;181(2):115-29 (Pubitemid 36629234)
13. Rossi F, Gianola S, Corvetti L. Regulation of intrinsic neuronal properties for axon growth and regeneration. Prog Neurobiol 2007;81(1):1-28 (Pubitemid 46282271)
14. He Z, Koprivica V. The Nogo signaling pathway for regeneration block. Annu Rev Neurosci 2004;27:341-68 (Pubitemid 39050407)
15. Ribotta MG, Menet V, Privat A. Glial scar and axonal regeneration in the CNS: lessons from GFAP and vimentin transgenic mice. Acta Neurochir Suppl 2004;89:87-92
16. Silver J, Miller JH. Regeneration beyond the glial scar. Nat Rev Neurosci 2004;5(2):146-56 (Pubitemid 38160289)
17. Yiu G, He Z. Glial inhibition of CNS axon regeneration. Nat Rev Neurosci 2006;7(8):617-27 (Pubitemid 44106744)
18. Chen MS, Huber AB, van der Haar ME, et al. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 2000;403(6768):434-9 (Pubitemid 30073093)
19. GrandPre T, Nakamura F, Vartanian T, Strittmatter SM. Identification of the nogo inhibitor of axon regeneration as a reticulon protein. Nature 2000;403(6768):439-44 (Pubitemid 30073094)
20. Prinjha R, Moore SE, Vinson M, et al. Inhibitor of neurite outgrowth in humans. Nature 2000;403(6768):383-4 (Pubitemid 30073077)
21. DeBellard ME, Tang S, Mukhopadhyay G, et al. Myelin-associated glycoprotein inhibits axonal regeneration from a variety of neurons via interaction with a sialoglycoprotein. Mol Cell Neurosci 1996;7(2):89-101 (Pubitemid 26147289)
22. Mukhopadhyay G, Doherty P, Walsh FS, et al. A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 1994;13(3):757-67 (Pubitemid 24300179)
23. Domeniconi M, Filbin MT. Overcoming inhibitors in myelin to promote axonal regeneration. J Neurol Sci 2005;233(1-2):43-7 (Pubitemid 40804814)
24. Yiu G, He Z. Signaling mechanisms of the myelin inhibitors of axon regeneration. Curr Opin Neurobiol 2003;13(5):545-51 (Pubitemid 37441273)
25. Di Giovanni S. Regeneration following spinal cord injury, from experimental models to humans: where are we? Expert Opin Ther Targets 2006;10(3):363-76 (Pubitemid 43949951)
26. Harel NY, Strittmatter SM. Can regenerating axons recapitulate developmental guidance during recovery from spinal cord injury? Nat Rev Neurosci 2006;7(8):603-16 (Pubitemid 44106743)
27. Teng FY, Tang BL. Axonal regeneration in adult CNS neurons-signaling molecules and pathways. J Neurochem 2006;96(6):1501-8 (Pubitemid 43351610)
28. Gris P, Murphy S, Jacob JE, et al. Differential gene expression profiles in embryonic, adult-injured and adult-uninjured rat spinal cords. Mol Cell Neurosci 2003;24(3):555-67 (Pubitemid 37506001)
29. Zhou FQ, Snider WD. Intracellular control of developmental and regenerative axon growth. Philos Trans R Soc Lond B Biol Sci 2006;361(1473):1575-92 (Pubitemid 44450212)
30. Emery DL, Royo NC, Fischer I, et al. Plasticity following injury to the adult central nervous system: is recapitulation of a developmental state worth promoting? J Neurotrauma 2003;20(12):1271-92 (Pubitemid 38018365)
31. Makwana M, Raivich G. Molecular mechanisms in successful peripheral regeneration. FEBS J 2005;272(11):2628-38 (Pubitemid 40825411)
32. Carmichael ST. Cellular and molecular mechanisms of neural repair after stroke: making waves. Ann Neurol 2006;59(5):735-42 (Pubitemid 43673150)
33. Carmichael ST, Archibeque I, Luke L, et al. Growth-associated gene expression after stroke: evidence for a growth-promoting region in peri-infarct cortex. Exp Neurol 2005;193(2):291-311 (Pubitemid 40616180)
34. Plunet W, Kwon BK, Tetzlaff W. Promoting axonal regeneration in the central nervous system by enhancing the cell body response to axotomy. J Neurosci Res 2002;68(1):1-6 (Pubitemid 34274991)
35. Tetzlaff W, Kobayashi NR, Giehl KM, et al. Response of rubrospinal and corticospinal neurons to injury and neurotrophins. Prog Brain Res 1994;103:271-86
36. Hendriks WT Eggers R, Ruitenberg MJ, et al. Profound differences in spontaneous long-term functional recovery after defined spinal tract lesions in the rat. J Neurotrauma 2006;23(1):18-35 (Pubitemid 43191084)
37. Kim JE, Li S, GrandPré T, et al. Axon regeneration in young adult mice lacking nogo-A/B. Neuron 2003;38(2):187-99 (Pubitemid 36555646)
38. Lee JK, Kim JE, Sivula M, Strittmatter SM. Nogo receptor antagonism promotes stroke recovery by enhancing axonal plasticity. J Neurosci 2004;24(27):6209-17 (Pubitemid 38891112)
39. Raineteau O, Fouad K, Bareyre FM, Schwab ME. Reorganization of descending motor tracts in the rat spinal cord. Eur J Neurosci 2002;16(9):1761-71 (Pubitemid 35370709)
40. Fernandes KJ, Fan DP, Tsui BJ, et al. Influence of the axotomy to cell body distance in rat rubrospinal and spinal motoneurons: differential regulation of GAP-43, tubulins, and neurofilament-M. J Comp Neurol 1999;414(4):495-510 (Pubitemid 29506362)
41. Jin Y, Fischer I, Tessler A, Houle JD. Transplants of fibroblasts genetically modified to express BDNF promote axonal regeneration from supraspinal neurons following chronic spinal cord injury. Exp Neurol 2002;177(1):265-75 (Pubitemid 35356839)
42. Tobias CA, Shumsky JS, Shibata M, et al. Delayed grafting of BDNF and NT-3 producing fibroblasts into the injured spinal cord stimulates sprouting, partially rescues axotomized red nucleus neurons from loss and atrophy, and provides limited regeneration. Exp Neurol 2003;184(1):97-113 (Pubitemid 37444023)
43. Saruhashi Y, Young W, Perkins R. The recovery of 5-HT immunoreactivity in lumbosacral spinal cord and locomotor function after thoracic hemisection. Exp Neurol 1996;139(2):203-13 (Pubitemid 26228089)
44. Camand E, Morel MP, Faissner A, et al. Long-term changes in the molecular composition of the glial scar and progressive increase of serotoninergic fibre sprouting after hemisection of the mouse spinal cord. Eur J Neurosci 2004;20(5):1161-76 (Pubitemid 39233570)
45. Tetzlaff W, Alexander SW, Miller FD, Bisby MA. Response of facial and rubrospinal neurons to axotomy: changes in mRNA expression for cytoskeletal proteins and GAP-43. J Neurosci 1991;11(8):2528-44
46. Miller FD, Tetzlaff W, Bisby MA, et al. Rapid induction of the major embryonic a-tubulin mRNA, Ta1, during nerve regeneration in adult rats. J Neurosci 1989;9(4):1452-63 (Pubitemid 19116763)
47. McGraw J, Oschipok LW, Liu J, et al. Galectin-1 expression correlates with the regenerative potential of rubrospinal and spinal motoneurons. Neuroscience 2004;128(4):713-9 (Pubitemid 39298424)
48. Jenkins R, Tetzlaff W, Hunt SP. Differential expression of immediate early genes in rubrospinal neurons following axotomy in rat. Eur J Neurosci 1993;5(3):203-9 (Pubitemid 23108573)
49. Alonso G, Ridet JL, Oestreicher AB, et al. B-50 (GAP-43) immunoreactivity is rarely detected within intact catecholaminergic and serotonergic axons innervating the brain and spinal cord of the adult rat, but is associated with these axons following lesion. Exp Neurol 1995;134(1):35-48
50. Storer PD, Dolbeare D, Houle JD. Treatment of chronically injured spinal cord with neurotrophic factors stimulates bII-tubulin and GAP-43 expression in rubrospinal tract neurons. J Neurosci Res 2003;74(4):502-11 (Pubitemid 37352072)
51. Storer PD, Houle JD. bII-tubulin and GAP 43 mRNA expression in chronically injured neurons of the red nucleus after a second spinal cord injury. Exp Neurol 2003;183(2):537-47 (Pubitemid 37205096)
52. Mason MR, Lieberman AR, Anderson PN. Corticospinal neurons up-regulate a range of growth-associated genes following intracortical, but not spinal, axotomy. Eur J Neurosci 2003;18(4):789-802 (Pubitemid 37059689)
53. Schreyer DJ, Skene JH. Injury-associated induction of GAP-43 expression displays axon branch specificity in rat dorsal root ganglion neurons. J Neurobiol 1993;24(7):959-70 (Pubitemid 23178785)
54. Neumann S, Woolf CJ. Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron 1999;23(1):83-91 (Pubitemid 29262466)
55. Starkey ML, Davies M, Yip PK, et al. Expression of the regeneration-associated protein SPRR1A in primary sensory neurons and spinal cord of the adult mouse following peripheral and central injury. J Comp Neurol 2009;513(1):51-68
56. Chong MS, Reynolds ML, Irwin N, et al. GAP-43 expression in primary sensory neurons following central axotomy. J Neurosci 1994;14(7):4375-84 (Pubitemid 24200559)
57. Mason MR, Lieberman AR, Grenningloh G, Anderson PN. Transcriptional upregulation of SCG10 and CAP-23 is correlated with regeneration of the axons of peripheral and central neurons in vivo. Mol Cell Neurosci 2002;20(4):595-615
58. Zhang Y, Roslan R, Lang D, et al. Expression of CHL1 and L1 by neurons and glia following sciatic nerve and dorsal root injury. Mol Cell Neurosci 2000;16(1):71-86 (Pubitemid 30616559)
59. Tonra JR, Curtis R, Wong V, et al. Axotomy upregulates the anterograde transport and expression of brain-derived neurotrophic factor by sensory neurons. J Neurosci 1998;18(11):4374-83 (Pubitemid 28243830)
60. Neumann S, Bradke F, Tessier-Lavigne M, Basbaum AI. Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron 2002;34(6):885-93 (Pubitemid 34722279)
61. Qiu J, Cai D, Dai H, et al. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 2002;34(6):895-903 (Pubitemid 34722280)
62. Goldberg JL, Klassen MP, Hua Y, Barres BA. Amacrine-signaled loss of intrinsic axon growth ability by retinal ganglion cells. Science 2002;296(5574):1860-4 (Pubitemid 34596271)
63. Leon S, Yin Y, Nguyen J, et al. Lens injury stimulates axon regeneration in the mature rat optic nerve. J Neurosci 2000;20(12):4615-26 (Pubitemid 30396627)
64. Fischer D, Petkova V, Thanos S, Benowitz LI. Switching mature retinal ganglion cells to a robust growth state in vivo: gene expression and synergy with RhoA inactivation. J Neurosci 2004 24(40) 8726-40. (Pubitemid 39362968)
65. Yin Y, Henzl MT, Lorber B, et al. Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nat Neurosci 2006;9(6):843-52
66. Muller A, Hauk TG, Fischer D. Astrocyte-derived CNTF switches mature RGCs to a regenerative state following inflammatory stimulation. Brain 2007;130(Pt 12):3308-20 (Pubitemid 350209074)
67. Raivich G, Bohatschek M, Da Costa C, et al. The AP-1 transcription factor c-Jun is required for efficient axonal regeneration. Neuron 2004;43(1):57-67 (Pubitemid 38952819)
68. Zhou FQ, Walzer MA, Snider WD. Turning on the machine: genetic control of axon regeneration by c-Jun. Neuron 2004;43(1):1-2 (Pubitemid 38952813)
69. Knoops B, Octave JN. a1-tubulin mRNA level is increased during neurite outgrowth of NG 108-15 cells but not during neurite outgrowth inhibition by CNS myelin. Neuroreport 1997;8(3):795-8 (Pubitemid 27128239)
70. Gloster A, Wu W, Speelman A, et al. The Ta1 a-tubulin promoter specifies gene expression as a function of neuronal growth and regeneration in transgenic mice. J Neurosci 1994;14(12):7319-30 (Pubitemid 24379743)
71. Di Giovanni S, De Biase A, Yakovlev A, et al. In vivo and in vitro characterization of novel neuronal plasticity factors identified following spinal cord injury. J Biol Chem 2005;280(3):2084-91
72. Tucker RP. The roles of microtubule-associated proteins in brain morphogenesis: a review. Brain Res Brain Res Rev 1990;15(2):101-20
73. Laux T, Fukami K, Thelen M, et al. GAP43, MARCKS, and CAP23 modulate PI(4,5)P2 at plasmalemmal rafts, and regulate cell cortex actin dynamics through a common mechanism. J Cell Biol 2000;149(7):1455-72
74. Frey D, Laux T, Xu L, et al. Shared and unique roles of CAP23 and GAP43 in actin regulation, neurite outgrowth, and anatomical plasticity. J Cell Biol 2000;149(7):1443-54
75. Caroni P, Grandes P. Nerve sprouting in innervated adult skeletal muscle induced by exposure to elevated levels of insulin-like growth factors. J Cell Biol 1990;110(4):1307-17
76. Aigner L, Arber S, Kapfhammer JP, et al. Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice. Cell 1995;83(2):269-78
77. Aigner L, Caroni P. Depletion of 43-kD growth-associated protein in primary sensory neurons leads to diminished formation and spreading of growth cones. J Cell Biol 1993;123(2):417-29 (Pubitemid 23313965)
78. Jung M, Petrausch B, Stuermer CA. Axon-regenerating retinal ganglion cells in adult rats synthesize the cell adhesion molecule L1 but not TAG-1 or SC-1. Mol Cell Neurosci 1997;9(2):116-31 (Pubitemid 27342643)
79. Klocker N, Jung M, Stuermer CA, Bähr M. BDNF increases the number of axotomized rat retinal ganglion cells expressing GAP-43, L1, and TAG-1 mRNA-a supportive role for nitric oxide? Neurobiol Dis 2001;8(1):103-13 (Pubitemid 32171822)
80. Walsh FS, Doherty P. Cell adhesion molecules and neuronal regeneration. Curr Opin Cell Biol 1996;8(5):707-13 (Pubitemid 26381729)
81. Di Giovanni S, Faden AI, Yakovlev A, et al. Neuronal plasticity after spinal cord injury: identification of a gene cluster driving neurite outgrowth. FASEB J 2005;19(1):153-4 (Pubitemid 40069949)
82. Naeve GS, Ramakrishnan M, Kramer R, et al. Neuritin: a gene induced by neural activity and neurotrophins that promotes neuritogenesis. Proc Natl Acad Sci USA 1997;94(6):2648-53 (Pubitemid 27136930)
83. Kimura K, Mizoguchi A, Ide C. Regulation of growth cone extension by SNARE proteins. J Histochem Cytochem 2003;51(4):429-33 (Pubitemid 36418039)
84. Bonilla IE, Tanabe K, Strittmatter SM. Small proline-rich repeat protein 1A is expressed by axotomized neurons and promotes axonal outgrowth. J Neurosci 2002;22(4):1303-15 (Pubitemid 34163732)
85. Caroni P. New EMBO members' review: actin cytoskeleton regulation through modulation of PI(4,5)P2 rafts. EMBO J 2001;20(16):4332-6 (Pubitemid 32772026)
86. Spencer T, Filbin MT. A role for cAMP in regeneration of the adult mammalian CNS. J Anat 2004;204(1):49-55 (Pubitemid 38128574)
87. Gao Y, Deng K, Hou J, et al. Activated CREB is sufficient to overcome inhibitors in myelin and promote spinal axon regeneration in vivo. Neuron 2004;44(4):609-21 (Pubitemid 39531226)
88. Cai D, Deng K, Mellado W, et al. Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro. Neuron 2002;35(4):711-9
89. Nikulina E, Tidwell JL, Dai HN, et al. The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery. Proc Natl Acad Sci USA 2004;101(23):8786-90 (Pubitemid 38745849)
90. Lindwall C, Kanje M: The role of p-c-Jun in survival and outgrowth of developing sensory neurons. Neuroreport 2005;16(15):1655-9 (Pubitemid 41805798)
91. Lindwall C, Dahlin L, Lundborg G, Kanje M. Inhibition of c-Jun phosphorylation reduces axonal outgrowth of adult rat nodose ganglia and dorsal root ganglia sensory neurons. Mol Cell Neurosci 2004;27(3):267-79 (Pubitemid 39433841)
92. Herdegen T, Skene P, Bahr M. The c-Jun transcription factor-bipotential mediator of neuronal death, survival and regeneration. Trends Neurosci 1997;20(5):227-31 (Pubitemid 27158053)
93. Seijffers R, Allchorne AJ, Woolf CJ. The transcription factor ATF-3 promotes neurite outgrowth. Mol Cell Neurosci 2006;32(1-2):143-54 (Pubitemid 43868103)
94. Campbell G, Hutchins K, Winterbottom J, et al. Upregulation of activating transcription factor 3 (ATF3) by intrinsic CNS neurons regenerating axons into peripheral nerve grafts. Exp Neurol 2005;192(2):340-7 (Pubitemid 40341679)
95. Pearson AG, Gray CW, Pearson JF, et al. ATF3 enhances c-Jun-mediated neurite sprouting. Brain Res Mol Brain Res 2003;120(1):38-45 (Pubitemid 37506070)
96. Fujitani M, Yamagishi S, Che YH, et al. P311 accelerates nerve regeneration of the axotomized facial nerve. J Neurochem 2004;91(3):737-44 (Pubitemid 39431166)
97. Di Giovanni S, Knights CD, Rao M, et al. The tumor suppressor protein p53 is required for neurite outgrowth and axon regeneration. EMBO J 2006;25(17):4084-96 (Pubitemid 44338749)
98. Tedeschi A, Nguyen T, Puttagunta R, et al. A p53-CBP/p300 transcription module is required for GAP-43 expression, axon outgrowth, and regeneration. Cell Death Differ 2008;16:543-54
99. Wong LF, Yip PK, Battaglia A, et al. Retinoic acid receptor b2 promotes functional regeneration of sensory axons in the spinal cord. Nat Neurosci 2006;9(2):243-50 (Pubitemid 43164548)
100. Yip PK, Wong LF, Pattinson D, et al. Lentiviral vector expressing retinoic acid receptor b2 promotes recovery of function after corticospinal tract injury in the adult rat spinal cord. Hum Mol Genet 2006;15(21):3107-18 (Pubitemid 44605493)
101. Pan W, Cain C, Yu Y, Kastin AJ. Receptor-mediated transport of LIF across blood-spinal cord barrier is upregulated after spinal cord injury. J Neuroimmunol 2006;174(1-2):119-25
102. Suzuki S, Yamashita T, Tanaka K, et al. Activation of cytokine signaling through leukemia inhibitory factor receptor (LIFR)/gp130 attenuates ischemic brain injury in rats. J Cereb Blood Flow Metab 2005;25(6):685-93 (Pubitemid 40705604)
103. Naumann T, Schnell O, Zhi Q, et al. Endogenous ciliary neurotrophic factor protects GABAergic, but not cholinergic, septohippocampal neurons following fimbria-fornix transection. Brain Pathol 2003;13(3):309-21 (Pubitemid 36975821)
104. Suzuki S, Tanaka K, Nogawa S, et al. Immunohistochemical detection of leukemia inhibitory factor after focal cerebral ischemia in rats. J Cereb Blood Flow Metab 2000;20(4):661-8 (Pubitemid 30217504)
105. Blesch A, Uy HS, Grill RJ, et al. Leukemia inhibitory factor augments neurotrophin expression and corticospinal axon growth after adult CNS injury. J Neurosci 1999;19(9):3556-66 (Pubitemid 29203135)
106. Guo X, Chandrasekaran V, Lein P, et al. Leukemia inhibitory factor and ciliary neurotrophic factor cause dendritic retraction in cultured rat sympathetic neurons. J Neurosci 1999;19(6):2113-21 (Pubitemid 29133389)
107. Kurek JB, Austin L, Cheema SS, et al. Up-regulation of leukaemia inhibitory factor and interleukin-6 in transected sciatic nerve and muscle following denervation. Neuromuscul Disord 1996;6(2):105-14 (Pubitemid 26073992)
108. Hakkoum D, Stoppini L, Muller D. Interleukin-6 promotes sprouting and functional recovery in lesioned organotypic hippocampal slice cultures. J Neurochem 2007;100(3):747-57 (Pubitemid 46095624)
109. Swartz KR, Liu F, Sewell D, et al. Interleukin-6 promotes post-traumatic healing in the central nervous system. Brain Res 2001;896(1-2):86-95 (Pubitemid 32244151)
110. Raivich G, Jones LL, Werner A, et al. Molecular signals for glial activation: pro-and anti-inflammatory cytokines in the injured brain. Acta Neurochir Suppl 1999;73:21-30
111. Banner LR, Patterson PH. Major changes in the expression of the mRNAs for cholinergic differentiation factor/leukemia inhibitory factor and its receptor after injury to adult peripheral nerves and ganglia. Proc Natl Acad Sci USA 1994;91(15):7109-13 (Pubitemid 24226812)
112. Bolin LM, Verity AN, Silver JE, et al. Interleukin-6 production by schwann cells and induction in sciatic nerve injury. J Neurochem 1995;64(2):850-8
113. Klein MA, Möller JC, Jones LL, et al. Impaired neuroglial activation in interleukin-6 deficient mice. Glia 1997;19(3):227-33 (Pubitemid 27140909)
114. Cafferty WB, Gardiner NJ, Gavazzi I, et al. Leukemia inhibitory factor determines the growth status of injured adult sensory neurons. J Neurosci 2001;21(18):7161-70 (Pubitemid 32846964)
115. Cafferty WB, Gardiner NJ, Das P, et al. Conditioning injury-induced spinal axon regeneration fails in interleukin-6 knock-out mice. J Neurosci 2004;24(18):4432-43 (Pubitemid 38608154)
116. Taga T. Gp130, a shared signal transducing receptor component for hematopoietic and neuropoietic cytokines. J Neurochem 1996;67(1):1-10 (Pubitemid 26185574)
117. Qiu J, Cafferty WB, McMahon SB, Thompson SW. Conditioning injury-induced spinal axon regeneration requires signal transducer and activator of transcription 3 activation. J Neurosci 2005;25(7):1645-53 (Pubitemid 40279269)
118. Bomze HM, Bulsara KR, Iskandar BJ, et al. Spinal axon regeneration evoked by replacing two growth cone proteins in adult neurons. Nat Neurosci 2001;4(1):38-43 (Pubitemid 32095524)
119. Zhang Y, Bo X, Schoepfer R, et al. Growth-associated protein GAP-43 and L1 act synergistically to promote regenerative growth of Purkinje cell axons in vivo. Proc Natl Acad Sci USA 2005;102(41):14883-8 (Pubitemid 41457150)
120. Gianola S, Rossi F. GAP-43 overexpression in adult mouse purkinje cells overrides myelin-derived inhibition of neurite growth. Eur J Neurosci 2004;19(4):819-30 (Pubitemid 38297019)
121. Sivasankaran R, Pei J, Wang KC, et al. PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration. Nat Neurosci 2004;7(3):261-8 (Pubitemid 38280450)
122. Benowitz LI, Goldberg DE, Madsen JR, et al. Inosine stimulates extensive axon collateral growth in the rat corticospinal tract after injury. Proc Natl Acad Sci USA 1999;96(23):13486-90
123. Chen P, Goldberg DE, Kolb B, et al. Inosine induces axonal rewiring and improves behavioral outcome after stroke. Proc Natl Acad Sci USA 2002;99(13):9031-6 (Pubitemid 34693678)
124. Bregman BS, Coumans JV, Dai HN, et al. Transplants and neurotrophic factors increase regeneration and recovery of function after spinal cord injury. Prog Brain Res 2002;137:257-73 (Pubitemid 35469060)
125. Kobayashi NR, Fan DP, Giehl KM, et al. BDNF and NT-4/5 prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Ta1-tubulin mRNA expression, and promote axonal regeneration. J Neurosci 1997;17(24):9583-95 (Pubitemid 28006402)
126. Ramer MS, Duraisingam I, Priestley JV, McMahon SB. Two-tiered inhibition of axon regeneration at the dorsal root entry zone. J Neurosci 2001;21(8):2651-60 (Pubitemid 32298207)
127. Hollis ER 2nd, Jamshidi P, Löw K, et al. Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation. Proc Natl Acad Sci USA 2009;106(17):7215-20
128. Park, KK, Liu K, Hu Y, et al. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 2008;322(5903):963-6
129. Hanz S, Fainzilber M. Retrograde signaling in injured nerve-the axon reaction revisited. J Neurochem 2006;99(1):13-9 (Pubitemid 44395126)
130. Tedeschi A, Di Giovanni S. The non-apoptotic role of p53 in neuronal biology: enlightening the dark side of the moon. EMBO Rep 2009;10(6):576-83
131. Dyke HJ, Montana JG. Update on the therapeutic potential of PDE4 inhibitors. Expert Opin Investig Drugs 2002;11(1):1-13 (Pubitemid 34048615)