Peptide mimetics of neurotrophins and their receptors

Current Pharmaceutical Design

Volumn 17, Issue 25, 2011, Pages 2704-2718

  Skaper, S D ^a  

^a UNIVERSITY OF PADOVA   (Italy)

Author keywords

Brain derived growth factor; Glial cell line derived neurotrophic factor; Nerve growth factor; Neuroprotection; Neuroregeneration; Neurotrophin 4 5; Neurotrophin 3; Receptor tyrosine kinases

Indexed keywords

NEUROTROPHIC FACTOR; NEUROTROPHIN; NEUROTROPHIN RECEPTOR; PEPTIDE DERIVATIVE;

ARTICLE; BLOOD BRAIN BARRIER; CELL DEATH; CELL SURVIVAL; CENTRAL NERVOUS SYSTEM DISEASE; DRUG COST; DRUG MANUFACTURE; HUMAN; NERVE CELL GROWTH; NERVE CELL LESION; NERVOUS SYSTEM DEVELOPMENT; NEUROPROTECTION; NONHUMAN; PERIPHERAL NERVOUS SYSTEM; PRIORITY JOURNAL;

EID: 80053537903     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161211797415995     Document Type: Article

References (244)

1. Sofroniew MV, Howe CL, Mobley WC. Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci 2001; 24: 1217-81.
2. Levi-Montalcini R. The nerve growth factor 35 years later. Science 1987; 237: 1154-62.
3. Levi-Montalcini R, Hamburger V. Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo. J Exp Zool 1951; 116: 321-61.
4. Levi-Montalcini R, Meyer H, Hamburger V. In vitro experiments on the effects of mouse sarcomas 180 and 37 on the spinal and sympathetic ganglia of the chick embryo. Cancer Res 1954; 14: 49-57.
5. Thoenen H. Neurotrophins and neuronal plasticity. Science 1995; 270: 593-8.
6. Thoenen H, Barde YA. Physiology of nerve growth factor. Physiol Rev 1980; 60: 1284-1335.
7. Barde YA. Trophic factors and neuronal survival. Neuron 1989; 2: 1525-34.
8. Hamburger V, Brunso-Bechthold JK, Yip JW. Neuronal death in the spinal ganglia of the chick embryo and its reduction by nerve growth factor. J Neurosci 1981; 1: 60-71.
9. Bothwell M. Functional interactions of neurotrophins and neurotrophin receptors. Annu Rev Neurosci 1995; 18: 223-53.
10. Hefti F. Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transactions. J Neurosci 1986; 6: 2155-62.
11. Williams LR, Varon S, Peterson GM, et al. Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transaction. Proc Natl Acad Sci USA 1986; 83: 9231-35.
12. Kordower JH, Emborg ME, Bloch J, et al. Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. Science 2000; 290: 767-73.
13. Grondin R, Zhang Z, Ai Y, Gash DM, Gerhardt GA. Intracranial delivery of proteins and peptides as a therapy for neurodegenerative diseases. Prog Drug Res 2003; 61: 101-23.
14. Ishii DN, Pu SF. In: Hefti F Ed, Neurotrophic Factors. Berlin, Springer. 1999; 119-46.
15. Sendtner M. In: Hefti F Ed, Neurotrophic Factors. Berlin, Springer. 1999; 81-117.
16. Schnell L, Schneider R, Kolbeck R, Barde YA. Neurotrophin-3 enhances sprouting of corticospinal tract during development and after spinal cord lesion. Nature 1994; 367: 170-3.
17. Kobayashi NR, Fan DP, Giehl KM, Bedard AM, Wiegand SJ, Tetzlaff W. BDNF and NT-4/5 prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Tα1-tubulin mRNA expression, and promote axonal regeneration. J Neurosci 1997; 17: 9583-95.
18. Ramer MS, Priestley JV, McMahon SB. Functional regeneration of sensory axons into the adult spinal cord. Nature 2000; 403: 312-6.
19. Oppenheim RW. Cell death during development of the nervous system. Annu Rev Neurosci 1991; 14: 453-501.
20. Barde YA, Edgar D, Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J 1982; 1: 549-53.
21. Leibrock J, Lottspeich F, Hohn A, et al. Molecular cloning and expression of brain-derived neurotrophic factor. Nature 1994; 341: 149-52.
22. Ernfors P, Ibáñez CF, Ebendal T, Olson L, Persson H. Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: developmental and topographical expression in the brain. Proc Natl Acad Sci USA 1990; 87: 5454-8.
23. Hohn A, Leibrock J, Bailey K, Barde YA. Identification and characterization of a novel member of the nerve growth factor/ brain-derived neurotrophic factor family. Nature 1990; 344: 339-41.
24. Jones KR, Reichardt LF. Molecular cloning of a human gene that is a member of the nerve growth factor family. Proc Natl Acad Sci USA 1990; 87: 8060-4.
25. Maisonpierre PC, Belluscio L, Squinto S, et al. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science 1990; 247: 1446-51.
26. Rosenthal A, Goeddel DV, Nguyen T, et al. Primary structure and biological activity of a novel human neurotrophic factor. Neuron 1990; 4: 767-73.
27. Negro A, Tavella A, Grandi C, Skaper SD. Production and characterization of recombinant rat brain-derived neurotrophic factor and neurotrophin-3 from insect cells. J Neurochem 1994; 62: 471-8.
28. Berkemeier LR, Winslow JW, Kaplan DR, Nicolics K, Goeddel DV, Rosenthal A. Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB. Neuron 1991; 7: 857-66.
29. Hallböök F, Ibáñez CF, Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron 1991; 6: 845-58.
30. Ip NY, Ibáñez CF, Nye SH, et al. Mammalian neurotrophin-4: structure, chromosomal localization, tissue distribution, and receptor specificity. Proc Natl Acad Sci USA 1992; 89: 3060-4.
31. Ip NY, Stitt TN, Tapley P, et al. Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells. Neuron 1993; 10: 137-49.
32. Götz R, Köster R, Winkler C, et al. Neurotrophin-6 is a new member of the nerve growth factor family. Nature 1994; 372: 266-269.
33. Lai KO, Fu WY, Ip FCF, Ip NY. Cloning and expression of a novel neurotrophin, NT-7, from carp. Mol Cell Neurosci 1998; 11: 64-76.
34. Eide FF, Lowenstein DH, Reichardt LF. Neurotrophins and their receptors--current concepts and implications for neurologic disease. Exp Neurol 1993; 121: 200-14.
35. Ibáñez CF. Neurotrophic factors: from structure-function studies to designing effective therapeutics. Trends Biotech 1995; 13: 217-27.
36. McDonald NQ, Lapatto R, Murray-Rust J, Gunning J, Wlodawer A, Blundell TL. New protein fold revealed by a 2.3-A resolution crystal structure of nerve growth factor. Nature 1991; 354: 411-4.
37. Holland DR, Cousens LS, Meng W, Matthews BW. Nerve growth factor in different crystal forms displays structural flexibility and reveals zinc binding sites. J Mol Biol 1994; 239: 385-400.
38. Robinson RC, Radziejewski C, Stuart DI, Jones EY. Structure of the brain-derived neurotrophic factor/neurotrophin 3 heterodimer. Biochemistry 1995; 34: 4139-46.
39. Butte MJ, Hwang PK, Mobley WC, Fletterick RJ. Crystal structure of neurotrophin-3 homodimer shows distinct regions are used to bind its receptors. Biochemistry 1998; 37: 16846-52.
40. Robinson RC, Radziejewski C, Spraggon G, et al. The structures of the neurotrophin 4 homodimer and the brain-derived neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding site. Protein Sci 1999; 8: 2589-97.
41. Wiesmann C, Ultsch MH, Bass SH, de Vos AM. Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor. Nature 1999; 401: 184-8.
42. Lindsay RM, Yancopoulos GD. GDNF in a bind with known orphan: accessory implicated in new twist. Neuron 1996; 17: 571-4.
43. Barde YA. Neurotrophic factors: an evolutionary perspective. J Neurobiol 1994; 25: 1329-33.
44. Kullander K, Carlson B, Hallböök FJ. Molecular phylogeny and evolution of the neurotrophins from monotremes and marsupials. Mol Evol 1997; 45: 311-21.
45. Butte MJ. Neurotrophic factor structures reveal clues to evolution, binding, specificity, and receptor activation. Cell Mol Life Sci 2001; 58: 1003-13.
46. Ip NY, Yancopoulos GD. The neurotrophins and CNTF: two families of collaborative neurotrophic factors. Annu Rev Neurosci 1996; 19: 491-15.
47. Doré S, Kar S, Quirion R. Rediscovering an old friend, IGF-I: potential use in the treatment of neurodegenerative diseases. Trends Neurosci 1997; 20: 326-31.
48. Walicke P, Cowan WM, Ueno N, Baird A, Guillemin R. Fibroblast growth factor promotes survival of dissociated hippocampal neurons and enhances neurite extension. Proc Natl Acad Sci USA 1986; 83: 3012-6.
49. Farkas LM, Dünker N, Roussa E Unsicker K, Krieglstein K. Transforming growth factor-βs are essential for the development of midbrain dopaminergic neurons in vitro and in vivo. J Neurosci 2003; 23: 5178-86.
50. Miao N Wang M, Ott JA, et al. Sonic hedgehog promotes the survival of specific CNS neuron populations and protects these cells from toxic insult In vitro. J Neurosci 1997; 17: 5891-9.
51. Radeke MJ, Misko TP, Hsu C, Herzenberg LA, Shooter E. Gene transfer and molecular cloning of the rat nerve growth factor receptor. Nature 1987; 325: 593-7.
52. Rodriguez-Tébar A, Dechant G, Barde YA. Binding of brainderived neurotrophic factor to the nerve growth factor receptor. Neuron 1990; 4: 487-92.
53. Rodríguez-Tébar A Dechant G, Götz R, Barde YA. Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor and brain-derived neurotrophic factor. EMBO J 1992; 11: 917-22.
54. He XE, Garcia KC. Structure of nerve growth factor complexed with the shared neurotrophin receptor p75. Science 2004; 304; 870-5.
55. Kaplan DR, Hempstead BL, Martin-Zanca D, Chao MV, Parada LF. The trk proto-oncogene product: a signal transducing receptor for nerve growth factor. Science 1991; 252: 554-8.
56. Kaplan DR, Martin-Zanca D, Parada LF. Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF. Nature 1991; 350: 158-60.
57. Klein R, Jing SQ, Nanduri V, O'Rourke E, Barbacid M. The trk proto-oncogene encodes a receptor for nerve growth factor. Cell 1991; 65: 189-97.
58. Klein R, Nanduri V, Jing SA, et al. The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Cell 1991; 66: 395-403.
59. Soppet D, Escandón E, Maragos J, et al. The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Cell 1991; 65: 895-903.
60. Squinto SP, Stitt TN, Aldrich TH, et al. trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor. Cell 1991; 65: 885-93.
61. Lamballe F, Klein R, Barbacid M. trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell 1991; 66: 967-79.
62. Cordon-Cardo C, Tapley P, Jing SQ, et al. The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3. Cell 1991; 66: 173-83.
63. Davies AM, Lee KF, Jaenisch R. p75-deficient trigeminal sensory neurons have an altered response to NGF but not to other neurotrophins. Neuron 1993; 11: 565-74.
64. Mahadeo D, Kaplan L, Chao MV, Hempstead BL. High affinity nerve growth factor binding displays a faster rate of association than p140trk binding. J Biol Chem 1994; 269: 6884-91.
65. Esposito D, Patel P, Stephens RM, et al. The cytoplasmic and transmembrane domains of the p75 and Trk A receptors regulate high affinity binding to nerve growth factor. J Biol Chem 2001; 276: 32687-95.
66. Ultsch MH, Wiesmann C, Simmons LC, et al. Crystal structures of the neurotrophin-binding domain of TrkA, TrkB and TrkC. J Mol Biol 1999; 290: 149-59.
67. Urfer R, Tsoulfas P, O'Connell L, Hongo JA, Zhao W, Presta LG. High resolution mapping of the binding site of TrkA for nerve growth factor and TrkC for neurotrophin-3 on the second immunoglobulin- like domain of the Trk receptors. J Biol Chem 1998; 273: 5829-40.
68. Wiesmann C, de Vos AM. Nerve growth factor: structure and function. Cell Mol Life Sci 2001; 58: 748-59.
69. Weiss A, Schlessinger J. Switching signals on or off by receptor dimerization. Cell 1998; 94: 277-80.
70. Huang EJ, Reichardt LF. Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem 2003; 72: 609-42.
71. Lee R, Kermani P, Teng KK, Hempstead BL. Regulation of cell survival by secreted proneurotrophins. Science 2001; 294: 1945-8.
72. Segal RA, Greenberg ME. Intracellular signaling pathways activated by neurotrophic factors. Annu Rev Neurosci 1996; 19: 463-89.
73. York RD, Molliver DC, Grewal SS, Stenberg PE, McCleskey EW, Stork PJS. Role of phosphoinositide 3-kinase and endocytosis in nerve growth factor-induced extracellular signal-regulated kinase activation via Ras and Rap1. Mol Cell Biol 2000; 20: 8069-83.
74. Yano H, Ninan I, Zhang H, Milner TA, Arancio O, Chao MV. BDNF-mediated neurotransmission relies upon a myosin VI motor complex. Nat Neurosci 2006; 9: 1009-18.
75. Lu B. BDNF and activity-dependent synaptic modulation. Learn Mem 2003; 10: 86-98.
76. Huang CS, Zhou J, Feng AK, et al. Nerve growth factor signaling in caveolae-like domains at the plasma membrane. J Biol Chem 1999; 274: 36707-14.
77. Shao Y, Akmentin W, Toledo-Aral JJ, et al. Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes. J Cell Biol 2002; 157: 679-91.
78. Delcroix JD, Valletta JS, Wu C, Hunt SJ, Kowal AS, Mobley WC. NGF signaling in sensory neurons: evidence that early endosomes carry NGF retrograde signals. Neuron 2003; 39: 69-84.
79. Arévalo JC, Waite J, Rajagopal R, et al. Cell survival through Trk neurotrophin receptors is differentially regulated by ubiquitination. Neuron 2006; 50: 549-59.
80. Tsui-Pierchala BA, Encinas M, Milbrandt J Johnson Jr EM. Trends Neurosci Lipid rafts in neuronal signaling and function. 2002; 25: 412-7.
81. Suzuki S, Numakawa T, Shimazu K, et al. BDNF-induced recruitment of TrkB receptor into neuronal lipid rafts: roles in synaptic modulation. J Cell Biol 2004; 167: 1205-15.
82. Pereira DB, Chao MV. The tyrosine kinase Fyn determines the localization of TrkB receptors in lipid rafts. J Neurosci 2007; 27: 4859-69.
83. Daub H, Weiss FU, Wallasch C, Ullrich A. Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature 1996: 379: 557-60.
84. Luttrell LM, Daaka Y, Lefkowitz RJ. Regulation of tyrosine kinase cascades by G-protein-coupled receptors. Curr Opin Cell Biol 1999; 11: 177-80.
85. Kotecha SA, Oak JN, Jackson MF, et al. A D2 class dopamine receptor transactivates a receptor tyrosine kinase to inhibit NMDA receptor transmission. Neuron 2002; 35: 1111-22.
86. Lee FS, Chao MV. Activation of Trk neurotrophin receptors in the absence of neurotrophins. Proc Natl Acad Sci USA 2001; 98: 3555-60.
87. Lee FS, Rajagopal R, Kim AH, Chang PC, Chao MV. Activation of Trk neurotrophin receptor signaling by pituitary adenylate cyclaseactivating polypeptides. J Biol Chem 2002; 277: 9096-9102.
88. Rajagopal R Chen ZY, Lee FS, Chao MV. Transactivation of Trk neurotrophin receptors by G-protein-coupled receptor ligands occurs on intracellular membranes. J Neurosci 2004; 24: 6650-8.
89. Rajagopal R, Chao MV. A role for Fyn in Trk receptor transactivation by G-protein-coupled receptor signaling. Mol Cell Neurosci 2006; 33: 36-46.
90. Sofroniew MV, Howe CL, Mobley WC. Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci 2001; 24: 1217-81.
91. Chao MV. Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci 2003; 4: 299-309.
92. Lu B, Pang PT, Woo NH. The yin and yang of neurotrophin action. Nat Rev Neurosci 2005; 6: 603-14.
93. Reichardt LF. Neurotrophin-regulated signalling pathways. Phil Trans Royal Soc B 2006; 361: 1545-64.
94. Björklund A, Rosenblad C, Winkler C, Kirik D. Studies on neuroprotective and regenerative effects of GDNF in a partial lesion model of Parkinson's disease. Neurobiology of Disease, 1997; 4: 186-200.
95. Gash DM, Zhang Z, Ovadia A, et al. Functional recovery in parkinsonian monkeys treated with GDNF. Nature 1996; 380: 252-5.
96. Biju K, Zhou Q, Li G, et al. Macrophage-mediated GDNF delivery protects against dopaminergic neurodegeneration: a therapeutic strategy for Parkinson's disease. Mol Ther (2010); doi:10.1038/mt.2010.107.
97. Yasuda T, Mochizuki H. Use of growth factors for the treatment of Parkinson's disease. Expert Rev Neurother 2010; 10: 915-24.
98. Lange DJ, Felice KJ, Festoff BW, et al. Recombinant human insulin- like growth factor-1 in ALS: description of a double-blind, placebo- controlled study. North American ALS/IGF-1 Study Group. Neurology 1996; 47: 93-4.
99. Borasio GD, Robberecht W, Leigh PN, et al. A placebo-controlled trial of insulin-like growth factor-1 in amytrophic lateral sclerosis. European ALS/IGF-1 Study Group.Neurology 1999; 51: 583-6.
100. A controlled trial of recombinant methionyl human BDNF in ALS. The BDNF study group (Phase III). Neurology 1999; 52: 1427-33.
101. Ochs G, Penn RD, York M, et al. A phase I/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 1: 201-6.
102. Beck M, Flachenecker P, Magnus T, et al. Autonomic dysfunction in ALS: a preliminary study on the effects of intrathecal BDNF. Amyotroph Lateral Scler Other Motor Neuron Disord 2005; 6: 100-3.
103. A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. ALS CNTF Treatment Study Group. Neurology 1996; 46: 1244-9.
104. Turner MR, Parton MJ, Leigh PN. Clinical trials in ALS: an overview. Seminars in Neurology 2001; 21: 167-75.
105. Nutt JG, Burchiel KD, Comella CL, et al. and the ICV GDNF Study Group. Randomized, double-blind trial of glial cell linederived neurotrophic factor (GDNF) in PD. Neurology 2003; 60: 69-73.
106. Lang AE, Gill S, Patel NK, et al. Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease. Ann Neurol 2006; 59: 459-66.
107. Podulso JF, Curran GL, Gill JS. Putrescine-modified nerve growth factor: bioactivity, plasma pharmacokinetics, blood-brain/nerve barrier permeability, and nervous system biodistribution. J Neurochem 1998; 71: 1651-60.
108. Wu D, Pardridge WM. Neuroprotection with noninvasive neurotrophin delivery to the brain. Proc Natl Acad Sci USA 1999; 96: 254-9.
109. Zhang Y, Pardridge WM. Neuroprotection in transient focal brain ischemia after delayed intravenous administration of brain-derived neurotrophic factor conjugated to a blood-brain barrier drug targeting system. Stroke 2001; 32: 1378-84.
110. Kotzbauer PT, Lampe PA, Heuckeroth RO, et al. Neurturin, a relative of glial-cell-line-derived neurotrophic factor. Nature 1996; 384: 467-70.
111. Choi-Lundberg DL, Lin Q, Chang YN, et al. Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 1997; 275: 838-41.
112. Fjord-Larsen L, Johansen JL, Kusk P, et al. Efficient in vivo protection of nigral dopaminergic neurons by lentiviral gene transfer of a modified Neurturin construct. Exp Neurol 2005; 195: 49-60.
113. Zhou L, Baumgartner BJ, Hill-Felberg SJ, McGowen LR, Shine HD. Neurotrophin-3 expressed in situ induces axonal plasticity in the adult injured spinal cord. J Neurosci 2003; 23: 1424-31.
114. Blesch A, Yang H, Weidner N, Hoang A, Otero D. Axonal responses to cellularly delivered NT-4/5 after spinal cord injury. Mol Cell Neurosci 2004; 27: 190-201.
115. Taylor L, Jones L, Tuszynski MH, Blesch A. Neurotrophin-3 gradients established by lentiviral gene delivery promote shortdistance axonal bridging beyond cellular grafts in the injured spinal cord. J Neurosci 2006; 26: 9713-21.
116. Tuszynski MH, Thal L, Pay M, et al. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med 2005; 11: 551-5.
117. Qu HY, Zhang T, Li XL, et al. Transducible P11-CNTF rescues the learning and memory impairments induced by amyloid-beta peptide in mice. Eur J Pharmacol 2008; 594: 93-100.
118. Garcia P, Youssef I, Utvik JK, et al. Ciliary neurotrophic factor cell-based delivery prevents synaptic impairment and improves memory in mouse models of Alzheimer's disease. J Neurosci 2010; 30: 7516-27.
119. Brewster WJ, Fernyhough P, Diemel LT, Mohiuddin L, Tomlinson RR. Diabetic neuropathy, nerve growth factor and other neurotrophic factors. Trends Neurosci 1994; 17: 321-5.
120. Anand P, Terenghi G, Warner G, Kopelman P, Williams-Chestnut RE, Sinicropi DV. The role of endogenous nerve growth factor in human diabetic neuropathy. Nat Med 1996; 2: 703-7.
121. Apfel SC. Nerve growth factor for the treatment of diabetic neuropathy: what went wrong, what went right, and what does the future hold? Internatl Rev Neurobiol 2002; 50: 393-413.
122. Apfel SC, Kessler JA, Adornato BT, Litchy WJ, Sanders C, Rask CA. Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy. NGF Study Group. Neurology 1998; 51: 695-702.
123. McArthur JC, Yiannoutsos C, Simpson DM, et al. A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. Neurology 2000; 54: 1080-8.
124. Apfel SC, Schwartz S, Adornato BT, et al. Efficacy and safety of human nerve growth factor in patients with diabetic polyneuropathy: A randomized controlled trial. J Am Med Assoc 2000; 284: 2215-21.
125. Schmidt RE, Dorsey DA, Beaudet LN, Parvin CA, Escandon E. Effect of NGF and neurotrophin-3 treatment on experimental diabetic autonomic neuropathy. J Neuropathol Exp Neurol 2001; 60: 263-73.
126. Lewin GR, Mendell LM. Nerve growth factor and nociception. Trends Neurosci 1993; 16: 353-9.
127. Calcutt NA, Allendoerfer KL, Mizisin AP, et al. Therapeutic efficacy of sonic hedgehog protein in experimental diabetic neuropathy. J Clin Invest 2003; 111: 507-14.
128. Mizisin AP, Vu Y, Shuff M, Calcutt NA. Ciliary neurotrophic factor improves nerve conduction and ameliorates regeneration deficits in diabetic rats. Diabetes 2004; 53: 1807-12.
129. Poduslo JF, Curran GL. Permeability at the blood-brain and bloodnerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF. Brain Res Mol Brain Res 1996; 36: 280-6.
130. Saragovi HU, Greene MI, Chrusciel RA, Kahn M. Loops and secondary structure mimetics: development and applications in basic science and rational drug design. Biotechnology 1992; 10: 773-8.
131. Wells JA. Hormone mimicry. Science 1996; 273: 449-50.
132. Williams WV, Moss DA, Kieber-Emmons T, et al. Development of biologically active peptides based on antibody structure. Proc Natl Acad Sci USA 1989; 86: 5537-41.
133. Williams WV, Kieber-Emmons T, VonFeldt J, Greene MI, Weiner DB. Design of bioactive peptides based on antibody hypervariable region structures. Development of conformationally constrained and dimeric peptides with enhanced affinity. J Biol Chem 1991; 266: 5182-90.
134. McDowell RS, Gadek TR. Structural studies of potent constrained RGD peptides. J Am Chem Soc 1992; 114: 9245-53.
135. Dechantsreiter MA, Planker E, Mathä B, et al. N-Methylated cyclic RGD peptides as highly active and selective alpha(V)beta(3) integrin antagonists. J Med Chem 1999; 42: 3033-40.
136. LeSauteur L, Wei L, Gibbs BF, Saragovi HU. Small peptide mimics of nerve growth factor bind TrkA receptors and affect biological responses. J Biol Chem 1995; 270: 6564-9.
137. Saragovi HU, Fitzpatrick D, Raktabuhr A, Nakanishi H, Kahn M, Green, MI. Design and synthesis of a mimetic of an antibody complementarity region. Science 1991; 253: 792-5.
138. LeSauteur L, Cheung NKV, Lisbona R, Saragovi HU. Small molecule nerve growth factor analogs image receptors in vivo. Nat Biotech 1996; 14: 1120-2.
139. Debeir T, Saragovi HU, Cuello AC. A nerve growth factor mimetic TrkA antagonist causes withdrawal of cortical cholinergic boutons in the adult rat. Proc Natl Acad Sci USA 1999; 96: 4067-72.
140. LeSauteur L, Maliartchouk S, Le Jeune H, Quirion R, Saragovi HU. Potent human p140-TrkA agonists derived from an antireceptor momoclonal antibody. J Neurosci 1996; 16: 1308-16.
141. Maliartchouk S, Debeir T, Beglova N, Cuello AC, Gehring K, Saragovi HU. Genuine monovalent ligands of TrkA nerve growth factor receptors reveal a novel pharmacological mechanism of action. J Biol Chem 2000; 275: 9946-56.
142. Xie Y, Tisi MA, Yeo TT, Longo FM. Nerve growth factor (NGF) loop 4 dimeric mimetics activate ERK and AKT and promote NGF-like neurotrophic effects. J Biol Chem 2000; 275: 29868-74.
143. Maliartchouk S, Feng Y, Ivanisevic L, et al. A designed peptidomimetic agonistic ligand of TrkA nerve growth factor receptors. Mol Pharmacol 2000; 57: 385-91.
144. Rashid K, Van der Zee CEEM, Ross GM, et al. A nerve growth factor peptide retards seizure development and inhibits neuronal sprouting in a rat model of epilepsy. Proc Natl Acad Sci USA 1995; 92: 9495-9.
145. Bruno MA, Clarke PBS, Seltzer A, et al. Long-lasting rescue of age-associated deficits in cognition and the CNS cholinergic phenotype by a partial agonist peptidomimetic ligand of TrkA. J Neurosci 2004; 24: 8009-18.
146. Burgess K. Solid phase syntheses of β-turn analogs designed to mimic or disrupt protein-protein interactions. Acc Chem Res 2001; 34: 826-35.
147. Zaccaro MC, Lee HB, Pattarawarapan M, et al. Selective small molecule peptidomimetic ligands of TrkC and TrkA receptors afford discrete or complete neurotrophic activities. Chem Biol 2005; 12: 1015-28.
148. Chen D, Brahimi F, Angell Y, et al. Bivalent peptidomimetic ligands of TrkC are biased agonists and selectively induce neuritogenesis or potentiate neurotrophin-3 signals. ACS Chemical Biol 2009; 4: 769-81 (doi: 10.1021/cb9001415).
149. Saragovi HU, Zheng W, Maliartchouk S, et al. A TrkA-selective, fast internalizing nerve growth factor-antibody complex induces trophic but not neuritogenic signals. J Biol Chem 1998; 273: 34933-40.
150. Saragovi HU, Gehring K. Development of pharmacological agents for targeting neurotrophins and their receptors. Trends Pharmacol Sci 2000; 3: 93-8.
151. Brahimi F, Malakhov A, Lee HB, et al. A peptidomimetic of NT-3 acts as a TrkC antagonist. Peptides 2009; 10: 1833-9.
152. McDonald NQ, Chao MV. Structural determinants of neurotrophin action. J Biol Chem 1995; 270: 19669-72.
153. Kahle P, Burton LE, Schmelzer CH, Hertel C. The amino terminus of nerve growth factor is involved in the interaction with the receptor tyrosine kinase p140trkA. J Biol Chem 1992; 267: 22707-10.
154. Shih A, Laramee GR, Schmelzer CH, Burton LE, Winslow JW. Mutagenesis identifies amino-terminal residues of nerve growth factor necessary for Trk receptor binding and biological activity. J Biol Chem 1994; 269: 27679-86.
155. Woo SB, Timm DE, Neet KE. Alteration of NH2-terminal residues of nerve growth factor affects activity and Trk binding without affecting stability or conformation. J Biol Chem 1995; 270: 6278-85.
156. Krüttgen A, Heymach JV Jr, Kahle PJ, Shooter EM. The role of the nerve growth factor carboxyl terminus in receptor binding and conformational stability. Biol Chem 1997; 272: 29222-28.
157. Rydén M, Ibàñez CF. A second determinant of binding to the p75 neurotrophin receptor revealed by alanine-scanning mutagenesis of a conserved loop in nerve growth factor. J Biol Chem 1997; 272: 33085-91.
158. Bradshaw RA, Murray-Rust J, Ibàñez CF, McDonald NQ, Lapatto R, Blundell TL. Nerve growth factor: structure/function relationship. Protein Sci 1994; 3: 1901-13.
159. Longo FM, Vu TK, Mobley WC. The in vitro biological effect of nerve growth factor is inhibited by synthetic peptides. Cell Reg 1990; 1: 189-95.
160. Longo FM, Manthorpe M, Xie YM, Varon S. Synthetic NGF peptide derivatives prevent neuronal death via a p75 receptordependent mechanism. J Neurosci Res 1997; 48: 1-17.
161. Estenne-Bouhtou G, Kullander K, Karlsson M, Ebendal T, Hacksell U, Luthman K. Design, synthesis, tandem mass spectrometric sequencing and biological activity of NGF mimetics. Int J Pept Protein Res 1996; 48: 337-46.
162. Colangelo AM, Bianco MR, Vitagliano L, et al. A new nerve growth factor-mimetic peptide active on neuropathic pain in rats. J Neurosci 2008; 28: 2698-709.
163. O'Leary PD, Hughes RA. Design of potent peptide mimetics of brain-derived neurotrophic factor. J Biol Chem 2003; 278: 25738-44.
164. O'Leary PD, Hughes RA. Structure-activity relationships of conformationally constrained peptide analogues of loop 2 of brainderived neurotrophic factor. J Neurochem 1998; 70: 1712-21.
165. Fletcher JM, Hughes RA. Novel monocyclic and bicyclic loop mimetics of brain-derived neurotrophic factor. J Pept Sci 2006; 12: 515-24.
166. Fletcher JM, Morton CJ, Zwar RA, Murray SS, O'Leary PD, Hughes RA. Design of a conformationally defined and proteolytically atable circular mimetic of brain-derived neurotrophic factor. J Biol Chem 2008; 283: 33375-83.
167. Fletcher JM, Hughes RA. Modified low molecular weight cyclic peptides as mimetics of BDNF with improved potency, proteolytic stability and transmembrane passage in vitro. Bioorg Med Chem 2009; 17: 2695-2702.
168. Zhang AJ, Khare S, Gokulan K, Linthicum DS, Burgess K. Dimeric β-turn peptidomimetics as ligands for the neurotrophin receptor TrkC. Bioorg Med Chem Lett 2003; 11: 207-10.
169. Williams G, Williams EJ, Maison P, Pangalos MN, Walsh F, Doherty P. Overcoming the inhibitors of myelin with a novel neurotrophin strategy. J Biol Chem 2005; 280: 5862-9.
170. Guillemard V, Ivanisevic L, Garcia AG, et al. An agonistic mAb directed to the TrkC receptor juxtamembrane region defines a trophic hot spot and interactions with p75 coreceptors. Dev Neurobiol 2010; 70: 150-64.
171. Massa SM, Yang T, Xie Y, et al. Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents. J Clin Invest 2010; 120: 1774-85.
172. Zhang Y, Chi XX, Nicol GD. BDNF enhances the excitability of rat sensory neurons through activation of the p75 neurotrophin receptor and the sphingomyelin pathway. J Physiol 2008; 586: 3113-27.
173. Kase H, Iwahashi K, Nakanishi S, et al. K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotidedependent protein kinases. Biochem Biophys Res Commun 1987;142: 436-40.
174. Matsuda Y, Nakanishi S, Nagasawa K, Iwahashi K, Kase H. The effect of K-252a, a potent microbial inhibitor of protein kinase, on activated cyclic nucleotide phosphodiesterase. Biochem J 1988; 256: 75-80.
175. Nye SH, Squinto SP, Glass DJ, et al. K-252a and staurosporine selectively block autophosphorylation of neurotrophin receptors and neurotrophin-mediated responses. Mol Cell Biol 1992; 3: 677-86.
176. Borasio, GD. Differential effects of the protein kinase inhibitor K-252a on the in vitro survival of chick embryonic neurons. Neurosci Lett 1990; 108: 207-12.
177. Knüsel B, Kaplan DR, Winslow JW, et al. K-252b selectively potentiates cellular actions and trk tyrosine phosphorylation mediated by NT-3. J Neurochem 1992; 59:715-22.
178. Manji, HK, Drevets WC, Charney DS. The cellular neurobiology of depression. Nat Med 2001; 7: 541-7.
179. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron 2002; 34: 13-25.
180. Castrén E, Võikar V, Rantamäki T. Role of neurotrophic factors in depression. Curr Opin Pharmacol 2007; 7: 18-21.
181. Eaton MJ, Whittemore SR. Autocrine BDNF secretion enhances the survival and serotonergic differentiation of raphe neuronal precursor cells grafted into the adult rat CNS. Exp Neurol 1996; 140: 105-14.
182. Mamounas LA, Blue ME, Siuciak JA, Altar CA. Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain. J Neurosci 1995; 15: 7929-39.
183. Nibuya M, Morinobu S, Duman RS. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 1995; 15: 7539-47.
184. Russo-Neustadt A, Beard RC, Cotman CW. Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression. Neuropsychopharmacology 1999; 21: 679-82.
185. Rantamäki T, Hendolin P, Kankaanpää A, et al. Pharmacologically diverse antidepressants rapidly activate brain-derived neurotrophic factor receptor TrkB and induce phospholipase-Cγ signaling pathways in mouse brain. Neuropsychopharmacology 2007; 32: 2152-62.
186. Roux P, Barker P. Neurotrophin signaling through the p75 neurotrophin receptor. Prog Neurobiol 2002; 67. 203-33.
187. Rabizadeh S, Oh J, Zhong LT, et al. Induction of apoptosis by the low-affinity NGF receptor. Science 1993; 261: 345-58.
188. Friedman WJ. Neurotrophins induce death of hippocampal neurons via the p75 receptor. J Neurosci 2000; 20: 6340-46.
189. Casaccia-Bonnefil P, Carter BD, Dobrowsky RT, Chao MV. Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75. Nature 1996; 383: 716-9.
190. Beattie MS, Harrington AW, Lee R, et al. ProNGF induces p75- mediated death of oligodendrocytes following spinal cord injury. Neuron 2002; 36: 375-86.
191. Harrington AW, Leiner B, Blechschmitt C, et al. Secreted proNGF is a pathophysiological death-inducing ligand after adult CNS injury. Proc Natl Acad Sci USA 2004; 101: 6226-30.
192. Nykjaer A, Lee R, Teng KK, et al. Sortilin is essential for proNGFinduced neuronal cell death. Nature 2004; 427: 843-8.
193. Fahnestock M, Michalski B, Xu B, Coughlin MD. The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer's disease. Mol Cell Neurosci 2001; 18: 210-20.
194. Volosin M, Song W, Almeida RD, Kaplan DR, Hempstead BL, Friedman WJ. Interaction of survival and death signaling in basal forebrain neurons: roles of neurotrophins and proneurotrophins. J Neurosci 2006; 26: 7756-66.
195. Carter BD, Kaltschmidt C, Kaltschmidt B, et al. Barde, Y.-A. (1996). Selective activation of NF-κB by nerve growth factor through the neurotrophin receptor p75. Science 1996; 272: 542-5.
196. NTR -mediated signaling promotes the survival of myoblasts and influences muscle strength. J Cell Physiol 2005; 204: 819-29.
197. Massa SM, Xie Y, Longo FM. Alzheimer's therapeutics: neurotrophin domain small molecule mimetics. Journal of Molecular Neuroscience 2003; 20: 323-6.
198. NTR ligands induce survival signaling and inhibit proNGF-induced death. J Neurosci 2006; 26: 5288-300.
199. NTR - dependent motor neuron death by a small non-peptidyl mimetic of the neurotrophin loop 1 domain. Eur J Neurosci 2006; 24: 1575-80.
200. Ferri CC, Moore FA, Bisby MA. Effects of facial nerve injury on mouse motoneurons lacking the p75 low-affinity neurotrophin receptor. J Neurobiol 1998; 34: 1-9.
201. Lowry KS, Murray SS, McLean CA, et al. A potential role for the p75 low-affinity neurotrophin receptor in spinal motor neuron degeneration in murine and human amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2001; 2: 127-34.
202. NTR in modulating neurotrophin survival effects in developing motoneurons. Eur J Neurosci 1999; 11: 1668-76.
203. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002; 297: 353-6.
204. Yaar M, Zhai S, Pilch PF, et al. Binding of β-amyloid to the p75 neurotrophin receptor induces apoptosis. A possible mechanism for Alzheimer's disease. J Clin Invest 1997; 100: 2333-40.
205. Costantini C, Rossi F, Formaggio E, Bernardoni R, Cecconi D, Della-Bianca V. Characterization of the signaling pathway down stream p75 neurotrophin reseptor involved in β-amyloid peptidedependent cell death. J Mol Neurosci 2005; 25: 141-56.
206. Coulson EJ. Does the p75 neurotrophin receptor mediate Aβ- induced toxicity in Alzheimer's disease? J Neurochem 2006; 98: 654-60.
207. Jung KM, Tan S, Landman N, et al. Regulated intramembrane proteolysis of the p75 neurotrophin receptor modulates its association with the TrkA receptor. J Biol Chem 2003; 278: 42161-9.
208. Kenchappa RS, Zampieri N, Chao MV, et al. Ligand-dependent cleavage of the p75 neurotrophin receptor is necessary for NRIF nuclear translocation and apoptosis in sympathetic neurons. Neuron 2006; 50: 219-32.
209. NTR and apoptosis. Am J Pathol 2006; 169: 119-31.
210. Coulson EJ, May LM, Osborne SI, et al. p75 neurotrophin receptor mediates neuronal cell death by activating GIRK channels through phosphatidylinositol 4,5-bisphosphate. J Neurosci 2008; 28: 315-24.
211. NTR promotes death signaling and is required for subsequent cleavage by γ-secretase. Mol Cell Neurosci 2008; 37: 346-58.
212. 1-42 induces neuronal death through the p75 neurotrophin receptor. J Neurosci 2008; 28: 3941-6.
213. NTR ligands inhibit Aβ-induced neurodegeneration and synaptic impairment. PloS ONE 3(11): e3604. doi:10.1371/journal.pone.0003604.
214. Qian MD, Zhang J, Tan XY, Wood A, Gill D, Cho S. Novel angonist monoclonal antibodies activate TrkB receptors and demonstrate potent neurotrophic activities. J Neurosci 2006; 26: 9394-9403.
215. NTR and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein. Nat Neurosci 2002; 5: 1302-8.
216. Skaper SD, Leon A, Toffano G. Ganglioside function in the development and repair of the mammalian nervous system: from basic science to clinical application. Mol Neurobiol 1989; 3: 173-99.
217. Ferrari G, Anderson BL, Stephens RM, Kaplan DR, Greene LA. Prevention of apoptotic neuronal death by GM1 ganglioside. Involvement of Trk neurotrophin receptors. J Biol Chem 1995; 270: 3074-80.
218. Mutoh T, Tokuda A, Miyadai T, Hamaguchi M, Fujiki N. Ganglioside GM1 binds to the Trk protein and regulates receptor function. Proc Natl Acad Sci USA 1995; 92: 5087-91.
219. Rabin SJ, Mocchetti I. GM1 ganglioside activates the high-affinity nerve growth factor receptor trkA. J Neurochem 1995; 65: 347-54.
220. Cuello AC, Garofalo L, Kenigsberg RL, Maysinger D. Gangliosides potentiate in vivo and in vitro effects of nerve growth factor on central cholinergic neurons. Proc Natl Acad Sci USA 1989; 86: 2056-60.
221. Fong TG, Vogelsberg V, Neff NH, Hadjiconstantinou M. GM1 and NGF synergism on choline acetyltransferase and choline uptake in aged brain. Neurobiol Aging 1995; 16: 917-23.
222. Fadda E, Negro A, Facci L, Skaper SD. Ganglioside GM1 cooperates with brain-derived neurotrophic factor to protect dopaminergic neurons from 6-hydroxydopamine-induced degeneration. Neurosci Lett 1993; 159: 147-50.
223. Skaper S.D, Negro A, Dal Toso R, Facci L. Recombinant human ciliary neurotrophic factor alters the threshold of hippocampal pyramidal neuron sensitivity to excitotoxin damage: synergisitc effects of monosialogangliosides. J Neurosci Res 1992; 33: 330-7.
224. Arakawa H, Iguchi T, Morita M, et al. Novel indolocarbazole compound 6-N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(β-Dglucopyranosyl)-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)- dione (NB-506): Its potent antitumor activities in mice. Cancer Res 1995; 55: 1316-20.
225. Yoshinari T, Matsumoto M, Arakawa H, et al. Novel antitumor indolocarbazole compound 6-N-formylamino-12,13-dihydro-1,11- dihydroxy-13-(beta-D-glucopyranosyl)-5H-indolo[2,3-a]pyrrolo [3,4- c]carbazole-5,7(6H)-dione (NB-506): induction of topoisomerase I-mediated DNA cleavage and mechanisms of cell lineselective cytotoxicity. Cancer Res 1995; 55: 1310-5.
226. Pollack S, Young L, Bilsland J, Wilkie N, Ellis S, Hefti F, Broughton H, Harper S. The staurosporine-like compound L-753,000 (NB-506) potentiates the neurotrophic effects of neurotrophin-3 by acting selectively at the TrkA receptor. Mol Pharmacol 1999; 56: 185-95.
227. Lewis MA, Hunihan L, Franco D, et al. Identification and characterization of compounds that potentiate NT-3-mediated Trk receptor activity. Mol Pharmacol 2006; 69: 1396-1404.
228. Skaper SD. Neuronal growth-promoting and inhibitory cues in neuroprotection and neuroregeneration. Ann NY Acad Sci 2005; 1053: 376-85.
229. Williams EJ, Furness J, Walsh FS, Doherty P. Activation of the FGF receptor underlies neurite outgrowth stimulated by L1, NCAM, and N-cadherin. Neuron 1994; 13: 583-94.
230. Rønn LCB, Olsen M, Østergaard S, et al. Identification of a neuritogenic ligand of the neural cell adhesion molecule using a combinatorial library of synthetic peptides. Nat Biotech 1999; 17: 1000-5.
231. Ditlevsen DK, Køhler LB, Pedersen MV, et al. The role of phosphatidylinositol 3-kinase in neural cell adhesion molecule-mediated neuronal differentiation and survival. J Neurochem 2003; 84: 546-56.
232. Ditlevsen DK, Berezin V, Bock E. Signalling pathways underlying neural cell adhesion molecule-mediated survival of dopaminergic neurons. Eur J Neurosci 2007; 25: 1678-84.
233. Williams E, Williams G, Gour BJ, Blaschuk OW, Doherty P. A novel family of cyclic peptide antagonists suggests that N-cadherin specificity is determined by amino acids that flank the HAV motif. J Biol Chem 2000; 275: 4007-12.
234. Williams G, Williams EJ, Doherty P. Dimeric versions of two short N-cadherin binding motifs (HAVDI and INPISG) function as Ncadherin agonists. J Biol Chem 2002; 277: 4361-7.
235. Skaper SD, Facci L, Williams G, Williams EJ, Walsh FS, Doherty P. A dimeric version of the short N-cadherin binding motif HAVDI promotes neuronal cell survival by activating an Ncadherin/ fibroblast growth factor receptor signalling cascade. Mol Cell Neurosci 2004; 26: 17-23.
236. Snider WD. Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 1994; 77: 627-38.
237. Jonsson E, Brené S, Zhang XR, et al. Schizophrenia and neurotrophin-3 alleles. Acta Psychiatr Scand 1997; 95: 414-9.
238. Thome J, Foley P, Riederer PJ. Neurotrophic factors and the maldevelopmental hypothesis of schizophrenic psychoses. Review article. Neural Transm 1998; 105: 85-100.
239. Kotzbauer PT, Holtzman DM. Expectations and challenges in the therapeutic use of neurotrophic factors. Ann Neurol 2006; 59: 444-7.
240. Zampieri N, Chao MV. Mechanisms of neurotrophin receptor signalling. Biochem Soc Trans 2006; 34: 607-11.
241. Peleshok J, Saragovi HU. Functional mimetics of neurotrophins and their receptors. Biochem Soc Trans 2006; 34: 612-7.
242. Pollack SJ, Harper SJ. Small molecule Trk receptor agonists and other neurotrophic factor mimetics. Curr Drug Targets - CNS & Neurol Disorders 2002; 1: 59-80.
243. Fitzgerald GA. Opinion: anticipating change in drug development: the emerging era of translational medicine and therapeutics. Nat Rev Drug Discov 2005; 4: 815-8.
244. Rose CR, Blum R, Pichler B, Lepier A, Kafitz KW, Konnerth A. Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia cells. Nature 2003; 426: 74-8.