Small molecule activators of the Trk receptors for neuroprotection

BMC Neuroscience

Volumn 9, Issue SUPPL. 2, 2008, Pages

  Webster, Nicholas J G ^a,b   Pirrung, Michael C ^c  

^a VETERANS AFFAIRS MEDICAL CENTER   (United States)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 FORMYLAMINO 12,13 DIHYDRO 1,11 DIHYDROXY 5H INDOLO[2,3 A]PYRROLO[3,4 C]CARBAZOLE 5,7(6H) DIONE 13 GLUCOSIDE; ACETYLCYSTEINE; AMIDE; AMPA RECEPTOR AGONIST; ASTERRIQUINONE DERIVATIVE; BMS 355249; BRAIN DERIVED NEUROTROPHIC FACTOR; BUTHIONINE SULFOXIMINE; CEP 1347; CEREBROLYSIN; GAMBOGIC AMIDE; K 252A; LETEPRINIM; N PEP 12; NERVE GROWTH FACTOR; NEUROTROPHIN; NEUROTROPHIN RECEPTOR; NORADRENALIN UPTAKE INHIBITOR; NORASTERRIQUINONE B1; PHOSPHOTRANSFERASE INHIBITOR; QUINONE DERIVATIVE; RECOMBINANT NERVE GROWTH FACTOR; RETINOID; SEROTONIN UPTAKE INHIBITOR; TRICYCLIC ANTIDEPRESSANT AGENT; TROPOMYOSIN RELATED KINASE RECEPTOR; TYROSINE KINASE RECEPTOR; UNCLASSIFIED DRUG; XALIPRODEN; LIGAND; NERVE GROWTH FACTOR RECEPTOR; NEUROPROTECTIVE AGENT;

ALZHEIMER DISEASE; CEREBROVASCULAR ACCIDENT; CLINICAL TRIAL; CONFERENCE PAPER; DRUG MECHANISM; DRUG PENETRATION; DRUG RESPONSE; EX VIVO GENE TRANSFER; GENE THERAPY; HUMAN; NEUROPROTECTION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; RISK FACTOR; TRAUMATIC BRAIN INJURY; ANIMAL; DRUG EFFECT; METABOLISM; NERVE CELL; NERVE DEGENERATION; REVIEW;

ALZHEIMER DISEASE; ANIMALS; HUMANS; LIGANDS; NERVE DEGENERATION; NEURONS; NEUROPROTECTIVE AGENTS; RECEPTORS, NERVE GROWTH FACTOR;

EID: 57449088366     PISSN: None     EISSN: 14712202     Source Type: Journal    
DOI: 10.1186/1471-2202-9-S2-S1     Document Type: Conference Paper

References (123)

1. Lanave C Colangelo AM Saccone C Alberghina L Molecular evolution of the neurotrophin family members and their Trk receptors Gene 2007, 394:1-12. 17379456
2. Dechant G Barde YA The neurotrophin receptor p75(NTR): Novel functions and implications for diseases of the nervous system Nat Neurosci 2002, 5:1131-1136. 12404007
3. Bothwell M Functional interactions of neurotrophins and neurotrophin receptors Annu Rev Neurosci 1995, 18:223-253. 7605062
4. Lewin GR Barde YA Physiology of the neurotrophins Annu Rev Neurosci 1996, 19:289-317. 8833445
5. Patapoutian A Reichardt LF Trk receptors: Mediators of neurotrophin action Curr Opin Neurobiol 2001, 11:272-280. 11399424
6. Hempstead BL Martin-Zanca D Kaplan DR Parada LF Chao MV High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor Nature 1991, 350:678-683. 1850821
7. Podlesniy P Kichev A Pedraza C Saurat J Encinas M Perez B Ferrer I Espinet C Pro-NGF from Alzheimer's disease and normal human brain displays distinctive abilities to induce processing and nuclear translocation of intracellular domain of p75NTR and apoptosis Am J Pathol 2006, 169:119-131. 1698760 16816366
8. Pedraza CE Podlesniy P Vidal N Arévalo JC Lee R Hempstead B Ferrer I Iglesias M Espinet C Pro-NGF isolated from the human brain affected by Alzheimer's disease induces neuronal apoptosis mediated by p75NTR Am J Pathol 2005, 166:533-543. 1602327 15681836
9. Friedman WJ Greene LA Neurotrophin signaling via Trks and p75 Exp Cell Res 1999, 253:131-142. 10579918
10. Kaplan DR Miller FD Neurotrophin signal transduction in the nervous system Curr Opin Neurobiol 2000, 10:381-391. 10851172
11. Kirstein M Farinas I Sensing life: Regulation of sensory neuron survival by neurotrophins Cell Mol Life Sci 2002, 59:1787-1802. 12530514
12. Harrison SM Davis BM Nishimura M Albers KM Jones ME Phillips HS Rescue of NGF-deficient mice I: Transgenic expression of NGF in skin rescues mice lacking endogenous NGF Brain Res Mol Brain Res 2004, 122:116-125. 15010204
13. Phillips HS Nishimura M Armanini MP Chen K Albers KM Davis BM Rescue of NGF-deficient mice II: Basal forebrain cholinergic projections require NGF for target innervation but not guidance Brain Res Mol Brain Res 2004, 124:1-11. 15093680
14. Chen KS Nishimura MC Armanini MP Crowley C Spencer SD Phillips HS Disruption of a single allele of the nerve growth factor gene results in atrophy of basal forebrain cholinergic neurons and memory deficits J Neurosci 1997, 17:7288-7296. 9295375
15. Jones KR Farinas I Backus C Reichardt LF Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development Cell 1994, 76:989-999. 8137432
16. Carroll P Lewin GR Koltzenburg M Toyka KV Thoenen H A role for BDNF in mechanosensation Nat Neurosci 1998, 1:42-46. 10195107
17. Korte M Carroll P Wolf E Brem G Thoenen H Bonhoeffer T Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor Proc Natl Acad Sci USA 1995, 92:8856-8860. 41066 7568031
18. Ernfors P Lee KF Kucera J Jaenisch R Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents Cell 1994, 77:503-512. 7514502
19. ElShamy WM Linnarsson S Lee KF Jaenisch R Ernfors P Prenatal and postnatal requirements of NT-3 for sympathetic neuroblast survival and innervation of specific targets Development 1996, 122:491-500. 8625800
20. Nosrat IV Lindskog S Seiger A Nosrat CA Lingual BDNF and NT-3 mRNA expression patterns and their relation to innervation in the human tongue: Similarities and differences compared with rodents J Comp Neurol 2000, 417:133-152. 10660893
21. Ockel M von Schack D Schropel A Dechant G Lewin GR Barde YA Roles of neurotrophin-3 during early development of the peripheral nervous system Philos Trans R Soc Lond B Biol Sci 1996, 351:383-387. 8730775
22. Quartu M Serra MP Manca A Follesa P Ambu R Del Fiacco M High affinity neurotrophin receptors in the human pre-term newborn, infant, and adult cerebellum Int J Dev Neurosci 2003, 21:309-320. 12927579
23. Aoki C Wu K Elste A Len G Lin S McAuliffe G Black IB Localization of brain-derived neurotrophic factor and TrkB receptors to postsynaptic densities of adult rat cerebral cortex J Neurosci Res 2000, 59:454-463. 10679783
24. Yan Q Radeke MJ Matheson CR Talvenheimo J Welcher AA Feinstein SC Immunocytochemical localization of TrkB in the central nervous system of the adult rat J Comp Neurol 1997, 378:135-157. 9120052
25. Crowley C Spencer SD Nishimura MC Chen KS Pitts-Meek S Armanini MP Ling LH McMahon SB Shelton DL Levinson AD et al Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons Cell 1994, 76:1001-1011. 8137419
26. Smeyne RJ Klein R Schnapp A Long LK Bryant S Lewin A Lira SA Barbacid M Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene Nature 1994, 368:246-249. 8145823
27. Fagan AM Garber M Barbacid M Silos-Santiago I Holtzman DM A role for TrkA during maturation of striatal and basal forebrain cholinergic neurons in vivo J Neurosci 1997, 17:7644-7654. 9315886
28. Schober A Minichiello L Keller M Huber K Layer PG Roig-López JL García-Arrarás JE Klein R Unsicker K Reduced acetylcholinesterase (AChE) activity in adrenal medulla and loss of sympathetic preganglionic neurons in TrkA-deficient, but not TrkB-deficient, mice J Neurosci 1997, 17:891-903. 8994044
29. Klein R Smeyne RJ Wurst W Long LK Auerbach BA Joyner AL Barbacid M Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death Cell 1993, 75:113-122. 8402890
30. Otal R Martinez A Soriano E Lack of TrkB and TrkC signaling alters the synaptogenesis and maturation of mossy fiber terminals in the hippocampus Cell Tissue Res 2005, 319:349-358. 15726425
31. Martínez A Alcántara S Borrell V Del Río JA Blasi J Otal R Campos N Boronat A Barbacid M Silos-Santiago I Soriano E TrkB and TrkC signaling are required for maturation and synaptogenesis of hippocampal connections J Neurosci 1998, 18:7336-7350. 9736654
32. Klein R Silos-Santiago I Smeyne RJ Lira SA Brambilla R Bryant S Zhang L Snider WD Barbacid M Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements Nature 1994, 368:249-251. 8145824
33. Halbach von Bohlen und O Minichiello L Unsicker K Haploinsufficiency for trkB and trkC receptors induces cell loss and accumulation of alpha-synuclein in the substantia nigra FASEB J 2005, 19:1740-1742. 16037097
34. Halbach von Bohlen und O Minichiello L Unsicker K Haploinsufficiency in trkB and/or trkC neurotrophin receptors causes structural alterations in the aged hippocampus and amygdala Eur J Neurosci 2003, 18:2319-2325. 14622193
35. Kahn MA Kumar S Liebl D Chang R Parada LF De Vellis J Mice lacking NT-3, and its receptor TrkC, exhibit profound deficiencies in CNS glial cells Glia 1999, 26:153-165. 10384880
36. Barker PA Lomen-Hoerth C Gensch EM Meakin SO Glass DJ Shooter EM Tissue-specific alternative splicing generates two isoforms of the trkA receptor J Biol Chem 1993, 268:15150-15157. 8325889
37. Tacconelli A Farina AR CappaL Desantis G Tessitore A Vetuschi A Sferra R Rucci N Argenti B Screpanti I et al TrkA alternative splicing: A regulated tumor-promoting switch in human neuroblastoma Cancer Cell 2004, 6:347-360. 15488758
38. Narumiya S Ohno M Tanaka N Yamano T Shimada M Enhanced expression of full-length TrkB receptors in young rat brain with hypoxic/ischemic injury Brain Res 1998, 797:278-286. 9666147
39. Hapner SJ Boeshore KL Large TH Lefcort F Neural differentiation promoted by truncated trkC receptors in collaboration with p75(NTR) Dev Biol 1998, 201:90-100. 9733576
40. Fryer RH Kaplan DR Kromer LF Truncated trkB receptors on nonneuronal cells inhibit BDNF-induced neurite outgrowth in vitro Exp Neurol 1997, 148:616-627. 9417837
41. Baxter GT Radeke MJ Kuo RC Makrides V Hinkle B Hoang R Medina-Selby A Coit D Valenzuela P Feinstein SC Signal transduction mediated by the truncated trkB receptor isoforms, trkB.T1 and trkB.T2 J Neurosci 1997, 17:2683-2690. 9092589
42. Bibel M Barde YA Neurotrophins: Key regulators of cell fate and cell shape in the vertebrate nervous system Genes Dev 2000, 14:2919-2937. 11114882
43. Thoenen H Neurotrophins and activity-dependent plasticity Prog Brain Res 2000, 128:183-191. 11105678
44. Huang EJ Reichardt LF Neurotrophins: Roles in neuronal development and function Annu Rev Neurosci 2001, 24:677-736. 11520916
45. Poo MM Neurotrophins as synaptic modulators Nat Rev Neurosci 2001, 2:24-32. 11253356
46. Winkler J Thal LJ Gage FH Fisher LJ Cholinergic strategies for Alzheimer's disease J Mol Med 1998, 76:555-567. 9694432
47. Horner PJ Gage FH Regenerating the damaged central nervous system Nature 2000, 407:963-970. 11069169
48. Naumann T Casademunt E Hollerbach E Hofmann J Dechant G Frotscher M Barde YA Complete deletion of the neurotrophin receptor p75NTR leads to long-lasting increases in the number of basal forebrain cholinergic neurons J Neurosci 2002, 22:2409-2418. 11923404
49. Troy CM Friedman JE Friedman WJ Mechanisms of p75-mediated death of hippocampal neurons. Role of caspases J Biol Chem 2002, 277:34295-34302. 12097334
50. Friedman WJ Neurotrophins induce death of hippocampal neurons via the p75 receptor J Neurosci 2000, 20:6340-6346. 10964939
51. Auld DS Kornecook TJ Bastianetto S Quirion R Alzheimer's disease and the basal forebrain cholinergic system: Relations to beta-amyloid peptides, cognition, and treatment strategies Prog Neurobiol 2002, 68:209-245. 12450488
52. Spranger M Lindholm D Bandtlow C Heumann R Gnahn H Näher-Noé M Thoenen H Regulation of nerve growth factor (NGF) synthesis in the rat central nervous system: Comparison between the effects of interleukin-1 and various growth factors in astrocyte cultures and in vivo Eur J Neurosci 1990, 2:69-76. 12106104
53. Peng S Wuu J Mufson EJ Fahnestock M Increased proNGF levels in subjects with mild cognitive impairment and mild Alzheimer disease J Neuropathol Exp Neurol 2004, 63:641-649. 15217092
54. Cuello AC Bruno MA The failure in NGF maturation and its increased degradation as the probable cause for the vulnerability of cholinergic neurons in Alzheimer's disease Neurochem Res 2007, 32:1041-1045. 17404842
55. Ginsberg SD Che S Wuu J Counts SE Mufson EJ Down regulation of trk but not p75NTR gene expression in single cholinergic basal forebrain neurons mark the progression of Alzheimer's disease J Neurochem 2006, 97:475-487. 16539663
56. Counts SE Nadeem M Wuu J Ginsberg SD Saragovi HU Mufson EJ Reduction of cortical TrkA but not p75(NTR) protein in early-stage Alzheimer's disease Ann Neurol 2004, 56:520-531. 15455399
57. Capsoni S Cattaneo A On the molecular basis linking nerve growth factor (NGF) to Alzheimer's disease Cell Mol Neurobiol 2006, 26:619-633. 16944323
58. Calamandrei G Pennazza S Ricceri L Valanzano A Neonatal exposure to anti-nerve growth factor antibodies affects exploratory behavior of developing mice in the hole board Neurotoxicol Teratol 1996, 18:141-146. 8709925
59. Garzon D Yu G Fahnestock M A new brain-derived neurotrophic factor transcript and decrease in brain-derived neurotrophic factor transcripts 1, 2 and 3 in Alzheimer's disease parietal cortex J Neurochem 2002, 82:1058-1064. 12358753
60. Fahnestock M Garzon D Holsinger RM Michalski B Neurotrophic factors and Alzheimer's disease: Are we focusing on the wrong molecule? J Neural Transm Suppl 2002, 62:241-252. 12456067
61. Berchtold NC Kesslak JP Cotman CW Hippocampal brain-derived neurotrophic factor gene regulation by exercise and the medial septum J Neurosci Res 2002, 68:511-521. 12111841
62. Ando S Kobayashi S Waki H Kon K Fukui F Tadenuma T Iwamoto M Takeda Y Izumiyama N Watanabe K Nakamura H Animal model of dementia induced by entorhinal synaptic damage and partial restoration of cognitive deficits by BDNF and carnitine J Neurosci Res 2002, 70:519-527. 12391613
63. Narisawa-Saito M Wakabayashi K Tsuji S Takahashi H Nawa H Regional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimer's disease Neuroreport 1996, 7:2925-2928. 9116211
64. Hock C Heese K Müller-Spahn F Huber P Riesen W Nitsch RM Otten U Increased cerebrospinal fluid levels of neurotrophin 3 (NT-3) in elderly patients with major depression Mol Psychiatry 2000, 5:510-513. 11032384
65. Murase K Igarashi K Hayashi K Neurotrophin-3 (NT-3) levels in the developing rat nervous system and in human samples Clin Chim Acta 1994, 227:23-36. 7955419
66. Chiaretti A Piastra M Polidori G Di Rocco C Caresta E Antonelli A Amendola T Aloe L Correlation between neurotrophic factor expression and outcome of children with severe traumatic brain injury Intensive Care Med 2003, 29:1329-1338. 12845427
67. Hicks RR Martin VB Zhang L Seroogy KB Mild experimental brain injury differentially alters the expression of neurotrophin and neurotrophin receptor mRNAs in the hippocampus Exp Neurol 1999, 160:469-478. 10619564
68. Felderhoff-Mueser U Sifringer M Pesditschek S Kuckuck H Moysich A Bittigau P Ikonomidou C Pathways leading to apoptotic neurodegeneration following trauma to the developing rat brain Neurobiol Dis 2002, 11:231-245. 12505417
69. Shetty AK Rao MS Hattiangady B Zaman V Shetty GA Hippocampal neurotrophin levels after injury: Relationship to the age of the hippocampus at the time of injury J Neurosci Res 2004, 78:520-532. 15468179
70. Rüttiger L Panford-Walsh R Schimmang T Tan J Zimmermann U Rohbock K Köpschall I Limberger A Müller M Fraenzer JT et al BDNF mRNA expression and protein localzation are changed in age-related hearing loss Neurobiol Aging 2007, 28:586-601. 16580094
71. Silhol M Bonnichon V Rage F Tapia-Arancibia L Age-related changes in brain-derived neurotrophic factor and tyrosine kinase receptor isoforms in the hippocampus and hypothalamus in male rats Neuroscience 2005, 132:613-624. 15837123
72. Royo NC Conte V Saatman KE Shimizu S Belfield CM Soltesz KM Davis JE Fujimoto ST McIntosh TK Hippocampal vulnerability following traumatic brain injury: A potential role for neurotrophin-4/5 in pyramidal cell neuroprotection Eur J Neurosci 2006, 23:1089-1102. 16553773
73. Grundy PL Patel N Harbuz MS Lightman SL Sharples PM Glucocorticoids modulate the NGF mRNA response in the rat hippocampus after traumatic brain injury Brain Res 2001, 892:386-390. 11172788
74. Grundy PL Patel N Harbuz MS Lightman SL Sharples PM Glucocorticoids modulate BDNF mRNA expression in the rat hippocampus after traumatic brain injury Neuroreport 2000, 11:3381-3384. 11059906
75. Chang CN Yang JT Lee TH Cheng WC Hsu YH Wu JH Dexamethasone enhances upregulation of nerve growth factor mRNA expression in ischemic rat brain J Clin Neurosci 2005, 12:680-684. 16115551
76. Yang JT Lee TH Weng HH Chang CN Chen WC Cheng WC Wu JH Dexamethasone enhances NT-3 expression in rat hippocampus after traumatic brain injury Exp Neurol 2005, 192:437-443. 15755560
77. Grundy PL Patel N Harbuz MS Lightman SL Sharples PM Adrenalectomy further suppresses the NT-3 mRNA response to traumatic brain injury but this effect is not reversed with corticosterone Brain Res Mol Brain Res 2004, 120:188-192. 14741409
78. Oudega M Hagg T Nerve growth factor promotes regeneration of sensory axons into adult rat spinal cord Exp Neurol 1996, 140:218-229. 8690064
79. Lu P Yang H Jones LL Filbin MT Tuszynski MH Combinatorial therapy with neurotrophins and cAMP promotes axonal regeneration beyond sites of spinal cord injury J Neurosci 2004, 24:6402-6409. 15254096
80. Pettigrew DB Li YQ Kuntz Ct Crutcher KA Global expression of NGF promotes sympathetic axonal growth in CNS white matter but does not alter its parallel orientation Exp Neurol 2007, 203:95-109. 16989811
81. Dinocourt C Gallagher SE Thompson SM Injury-induced axonal sprouting in the hippocampus is initiated by activation of trkB receptors Eur J Neurosci 2006, 24:1857-1866. 17040478
82. Hattiangady B Rao MS Zaman V Shetty AK Incorporation of embryonic CA3 cell grafts into the adult hippocampus at 4-months after injury: Effects of combined neurotrophic supplementation and caspase inhibition Neuroscience 2006, 139:1369-1383. 16580143
83. Royo NC Lebold D Magge SN Chen I Hauspurg A Cohen AS Watson DJ Neurotrophin-mediated neuroprotection of hippocampal neurons following traumatic brain injury is not associated with acute recovery of hippocampal function Neuroscience 2007, 148:359-370. 17681695
84. Sharma HS Neurotrophic factors attenuate microvascular permeability disturbances and axonal injury following trauma to the rat spinal cord Acta Neurochir Suppl 2003, 86:383-388. 14753473
85. Koponen E Rantamaki T Voikar V Saarelainen T MacDonald E Castren E Enhanced BDNF signaling is associated with an antidepressant-like behavioral response and changes in brain monoamines Cell Mol Neurobiol 2005, 25:973-980. 16392030
86. Saarelainen T Hendolin P Lucas G Koponen E Sairanen M MacDonald E Agerman K Haapasalo A Nawa H Aloyz R et al Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects J Neurosci 2003, 23:349-357. 12514234
87. Tuszynski MH Thal L Pay M Salmon DP U HS Bakay R Patel P Blesch A Vahlsing HL Ho G et al A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease Nat Med 2005, 11:551-555. 15852017
88. Shimoke K Chiba H Nerve growth factor prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced cell death via the Akt pathway by suppressing caspase-3-like activity using PC12 cells: relevance to therapeutical application for Parkinson's disease J Neurosci Res 2001, 63:402-409. 11223915
89. Thorne RG Frey WH 2nd Delivery of neurotrophic factors to the central nervous system: Pharmacokinetic considerations Clin Pharmacokinet 2001, 40:907-946. 11735609
90. Miller G Drug targeting. Breaking down barriers Science 2002, 297:1116-1118. 12183610
91. Gozes I Giladi E Pinhasov A Bardea A Brenneman DE Activity-dependent neurotrophic factor: Intranasal administration of femtomolar-acting peptides improve performance in a water maze J Pharmacol Exp Ther 2000, 293:1091-1098. 10869414
92. Thorne RG Emory CR Ala TA Frey WH 2nd Quantitative analysis of the olfactory pathway for drug delivery to the brain Brain Res 1995, 692:278-282. 8548316
93. Chen XQ Fawcett JR Rahman YE Ala TA Frey IW Delivery of nerve growth factor to the brain via the olfactory pathway J Alzheimers Dis 1998, 1:35-44. 12214010
94. Tuszynski MH Thal L U HS Pay MM Blesch A Conner J Vahlsing HL Nerve growth factor gene therapy for Alzheimer's disease J Mol Neurosci 2002, 19:207. 12212782
95. De Rosa R Garcia AA Braschi C Capsoni S Maffei L Berardi N Cattaneo A Intranasal administration of nerve growth factor (NGF) rescues recognition memory deficits in AD11 anti-NGF transgenic mice Proc Natl Acad Sci USA 2005, 102:3811-3816. 553297 15728733
96. Eriksdotter Jönhagen M Nordberg A Amberla K Bäckman L Ebendal T Meyerson B Olson L Seiger Shigeta M Theodorsson E et al Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer's disease Dement Geriatr Cogn Disord 1998, 9:246-257. 9701676
97. Saragovi HU Gehring K Development of pharmacological agents for targeting neurotrophins and their receptors Trends Pharmacol Sci 2000, 21:93-98. 10689362
98. Dagø L Bonde C Peters D Møller A Bomholt SF Hartz JB Meyer M Drejer J Grønborg M NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo J Neurochem 2002, 81:17-24. 12067229
99. 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, 275:29868-29874. 10896671
100. Zaccaro MC Lee HB Pattarawarapan M Xia Z Caron A L'Heureux PJ Bengio Y Burgess K Saragovi HU Selective small molecule peptidomimetic ligands of TrkC and TrkA receptors afford discrete or complete neurotrophic activities Chem Biol 2005, 12:1015-1028. 16183026
101. Peleshok J Saragovi HU Functional mimetics of neurotrophins and their receptors Biochem Soc Trans 2006, 34:612-617. 16856874
102. Massa SM Xie Y Yang T Harrington AW Kim ML Yoon SO Kraemer R Moore LA Hempstead BL Longo FM Small, nonpeptide p75NTR ligands induce survival signaling and inhibit proNGF-induced death J Neurosci 2006, 26:5288-5300. 16707781
103. Xie Y Massa SM Ensslen-Craig SE Major DL Yang T Tisi MA Derevyanny VD Runge WO Mehta BP Moore LA et al Protein-tyrosine phosphatase (PTP) wedge domain peptides: A novel approach for inhibition of PTP function and augmentation of protein-tyrosine kinase function J Biol Chem 2006, 281:16482-16492. 16613844
104. Alvarez XA Cacabelos R Laredo M Couceiro V Sampedro C Varela M Corzo L Fernandez-Novoa L Vargas M Aleixandre M et al A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease Eur J Neurol 2006, 13:43-54. 16420392
105. Price RD Milne SA Sharkey J Matsuoka N Advances in small molecules promoting neurotrophic function Pharmacol Ther 2007, 115:292-306. 17599430
106. Ramirez JJ Parakh T George MN Freeman L Thomas AA White CC Becton A The effects of Neotrofin on septodentate sprouting after unilateral entorhinal cortex lesions in rats Restor Neurol Neurosci 2002, 20:51-59. 12237496
107. Potkin SG Alva G Keator D Carreon D Fleming K Fallon JH Brain metabolic effects of Neotrofin in patients with Alzheimer's disease Brain Res 2002, 951:87-95. 12231461
108. Pradines A Magazin M Schiltz P Le Fur G Caput D Ferrara P Evidence for nerve growth factor-potentiating activities of the nonpeptidic compound SR 57746A in PC12 cells J Neurochem 1995, 64:1954-1964. 7722483
109. Wang LH Paden AJ Johnson EM Jr Mixed-lineage kinase inhibitors require the activation of Trk receptors to maintain long-term neuronal trophism and survival J Pharmacol Exp Ther 2005, 312:1007-1019. 15525794
110. 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, 56:185-195. 10385700
111. Roux PP Dorval G Boudreau M Angers-Loustau A Morris SJ Makkerh J Barker PA K252a and CEP1347 are neuroprotective compounds that inhibit mixed-lineage kinase-3 and induce activation of Akt and ERK J Biol Chem 2002, 277:49473-49480. 12388555
112. Lewis MA Hunihan L Franco D Robertson B Palmer J Laurent DR Balasubramanian BN Li Y Westphal RS Identification and characterization of compounds that potentiate NT-3-mediated Trk receptor activity Mol Pharmacol 2006, 69:1396-1404. 16399850
113. Bennett BM Reynolds JN Prusky GT Douglas RM Sutherland RJ Thatcher GR Cognitive deficits in rats after forebrain cholinergic depletion are reversed by a novel NO mimetic nitrate ester Neuropsychopharmacology 2007, 32:505-513. 16525416
114. Culmsee C Gerling N Landshamer S Rickerts B Duchstein HJ Umezawa K Klumpp S Krieglstein J Nitric oxide donors induce neurotrophin-like survival signaling and protect neurons against apoptosis Mol Pharmacol 2005, 68:1006-1017. 16027232
115. Akassoglou K Nerve growth factor-independent neuronal survival: A role for NO donors Mol Pharmacol 2005, 68:952-955. 16046659
116. Lee FS Rajagopal R Kim AH Chang PC Chao MV Activation of Trk neurotrophin receptor signaling by pituitary adenylate cyclase-activating polypeptides J Biol Chem 2002, 277: 9096-9102. 11784714
117. Lee FS Chao MV Activation of Trk neurotrophin receptors in the absence of neurotrophins Proc Natl Acad Sci USA 2001, 98:3555-3560. 30691 11248116
118. Kamata H Oka S Shibukawa Y Kakuta J Hirata H Redox regulation of nerve growth factor-induced neuronal differentiation of PC12 cells through modulation of the nerve growth factor receptor, TrkA Arch Biochem Biophys 2005, 434:16-25. 15629104
119. Jang SW Okada M Sayeed I Xiao G Stein D Jin P Ye K Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death Proc Natl Acad Sci USA 2007, 104:16329-16334. 2042206 17911251
120. Zhang B Salituro G Szalkowski D Li Z Zhang Y Royo I Vilella D Díez MT Pelaez F Ruby C et al Discovery of a small molecule insulin mimetic with antidiabetic activity in mice Science 1999, 284:974-977. 10320380
121. Liu K Xu L Szalkowski D Li Z Ding V Kwei G Huskey S Moller DE Heck JV Zhang BB Jones AB Discovery of a potent, highly selective, and orally efficacious small-molecule activator of the insulin receptor J Med Chem 2000, 43:3487-3494. 11000003
122. Air EL Strowski MZ Benoit SC Conarello SL Salituro GM Guan XM Liu K Woods SC Zhang BB Small molecule insulin mimetics reduce food intake and body weight and prevent development of obesity Nat Med 2002, 8:179-183. 11821903
123. Lin B Pirrung MC Deng L Li Z Liu Y Webster NJ Neuroprotection by small molecule activators of the nerve growth factor receptor J Pharmacol Exp Ther 2007, 322:59-69. 17468299