Neurotrophins

Abstract

Neurotrophins Neurotrophins are the family of growth factors polypeptides which regulate the survival and functions of neurons, synaptic plasticity and synaptic function. Members of the neurotrophin family are nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5, neurotrophin-6 and neurotrophin-7. Neurotrophins are synthesized by neurons of central and peripheral nervous system and many cell types of peripheral tissues and are known to have biological effects on the nervous system as well as in numerous tissues apart from of the nervous system. It is postulated that lack in synthesis of neurotrophins are related to increase susceptibility of neurodegenerative diseases. The therapeutic effects of neurotrophins for neurodegenerative disorders are being explored. The aim of this review is to present information about the structures, synthesizing cells, effect mechanisms and functions of neurotrophins.

Keywords

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Nörotrofinler

Abstract

Nörotrofinler, nöronların sağkalımını ve fonksiyonlarını etkileyen, sinaptik fonksiyonu ve sinaptik plastisiteyi kontrol eden polipeptid yapılı büyüme faktör ailesidir. Nörotrofin ailesi üyeleri, sinir büyüme faktörü, beyin kaynaklı nörotrofik faktör, nörotrofin-3, nörotrofin-4/5, nörotrofin-6, ve nörotrofin7’dir. Nörotrofinler, merkezi sinir sistemi, periferal sinir sistemi nöronları ve periferal dokulardaki birçok hücre tipinden sentezlenmektedir ve hem sinir sisteminde hem de sinir sistemi dışındaki pek çok dokuda biyolojik etkiye sahip oldukları bilinmektedir. Nörotrofin sentezindeki yetersizliğin nörodejeneratif hastalıklara duyarlılığın artışı ile ilgili olduğu kabul edilmektedir. Son yıllarda, nörotrofinlerin nörodejeneratif hastalıklarda tedavi edici etkisi araştırılmaktadır. Bu derlemenin amacı nörotrofinlerin yapıları, sentezlendiği hücreler, etki mekanizmaları ve fonksiyonları hakkında bilgi sunmaktır. ●●●

Keywords

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References

1. Acheson A, Barker PA, Alderson RF, Miller FD, Murphy RA. Detection of brain-derived neurotrophic factor-like activity in fibroblasts and Schwann cells: inhibition by antibodies to NGF. Neuron. 1991; 7:265-275.
2. Alderson RF, Alterman AL, Barde YA, Lindsay RM. Brain-derived neurotrophic factor increases survival and differentiated functions of rat septal cholinergic neurons in culture. Neuron. 1990; 5:297-306.
3. Aloe L, Bracci-Laudiero L, Bonini S, Manni L. The expanding role of nerve growth factor: from neurotrophic activity to immunologic diseases. Allergy. 1997; 52:883-894.
4. Aloe L, Rocco ML, Bianchi P, Manni L. Nerve growth factor: from the early discoveries to the potential clinical use. Trans Med. 2012; 10(239):1-15.
5. Angeletti RH, Bradshaw RA. The amino acid sequence of 2.5S mouse submaxillary gland nerve growth factor. Proc Natl Acad Sci. 1971; 68:2417-2420.
6. Anton ES, Weskamp G, Reichardt LF, Matthew WD. Nerve growth factor and its low affinity receptor promote Schwann cell migration. Proc Natl Acad Sci. 1994; 91:2795-2799.
7. Arenas E, Persson H. Neurotrophin-3 prevents the death of adult central noradrenergic neurons in vivo. Nature. 1994; 367:368-371.
8. Auffray I, Chevalier S, Froger J, Izac B, Vainchenker W, Gascan H, Coulombel L. Nerve growth factor is involved in the supportive effect by bone marrow-derived stromal cells of the factor-dependent human cell line UT-7. Blood. 1996; 88:1608-1618.

9. Barde YA, Edgar D, Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1982; 1(5):549-553.
10. Barres BA, Raff MC, Gaesse F, Bartke I, Dechant G, Barde YA. A crucial role for neurotrophin-3 in oligodendrocyte development. Nature. 1994; 367:371-375.
11. Bekinschtein P, Cammarota M, Izquierdo I, Medina JH. BDNF and Memory Formation and Storage. Neuroscientist. 2008; 14(2):1471
12. Berkemeier LR, Winslow JW, Kaplan DR. Nikolics K, Goeddel DV, Rosenthal A. Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB. Neuron .1991; 7:857-866.
13. Bischoff SC, Dahinden CA. Effect of nerve growth factor on the release of inflammatory mediators by mature human basophils. Blood .1992; 79:2662-2669.
14. Bradshaw RA, Murray-Rust J, Ibanez CF, McDonald NQ, Lapatto R, Blundell TL. Nerve growth factor: structure / function relationships. Protein Sci. 1994; 3:1901-1913.
15. Brodski C, Schnürch H, Dechant G. Neurotrophin-3 promotes the cholinergic differentiation of sympathetic neurons. PNAS. 2000; 97(17):9683-9688. Chalazonitis A. Neurotrophin-3 in the development of the enteric nervous system. Progress in Brain Research 146:243-263.
16. Chaldakov GN, Tonchev AB, Manni L. Comment on: Krabbe KS, Nielsen AR, Krogh-Madsen R. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia. 2007; 50:431-438.
17. Chao, MV. The p75 neurotrophin receptor. J Neurobiol. 1994; 25:1373-1385.
18. Cohen A, Bray GM, Aguayo AJ. Neurotrophin4/5 (NT- 4/5) increases adult rat retinal ganglion cell survival and neurite outgrowth in vitro. J Neurobiol. 1994; 25:953-959.
19. Cohen RI, Marmur R, Norton WT, Mehler MF, Kessler JA. Nerve Growth Factor and Neurotrophin-3 Differentially Regulate the Proliferation and Survival of Developing Rat Brain Oligodendrocytes. J Neurosci. 1996; 16(20):6433-6442.
20. Cristofaro B, Stone OA, Caporali A, Dawbarn D, Ieronimakis N, Reyes M, Madeddu P, Bates DO, Emanueli C. Neurotrophin-3 is a novel angiogenic factor capable of therapeutic neovascularization in a mouse model of limb ischemia. Arterioscler Thromb Vasc Biol. 2010; 30:1143-1150.
21. Davies AM, Horton A, Burton LE, Schmelzer C, Vandlen R, Rosenthal A. Neurotrophin-4/5 is a Mammalian-specific Survival Factor for Distinct Populations of Sensory Neurons. J Neurosci. 1993; 73(11):4961-4967.
22. 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.
23. Defazio RA, Pong K, Knusel B, Walsh JP. Neurotrophin-4/5 Promotes Dendritic Outgrowth and Calcium Currents in Cultured Mesencephalic Dopamine Neurons. J Neurosci. 2000; 99(2):297-304.
24. Elkabes S, DiCicco-Bloom EM, Black IB. Brain microglia/macrophages express neurotrophins that in selectively regulate microglial proliferation and function. J Neurosci. 1996; 16:2508-2521.
25. Eveleth DD. Nerve growth factor receptors: Structure and function. In Vitro Cell Dev Biol. 1988; 24:1148-1153.
26. Fawcett JP, Aloyz R, McLean JH, Pareek S, Miller FD, McPherson PS, Murphy RA. Detection of brain derived neurotrophic factor in a vesicular fraction of brain synaptosomes. J Biol Chem. 1997; 272:883788
27. Friedman WJ, Ibanez CF, Hallböök F, Persson H, Cain LD, Dreyfus CF, Black IB. Differential actions of neurotrophins in the locus coeruleus and basal forebrain. Exp Neurol. 1993; 119:72-78.
28. Ghosh A, Greenberg ME. Distinct roles for bFGF and NT-3 in the regulation of cortical neurogenesis. Neuron. 1995; 15:89-103.
29. Götz R, Köster R, Winkler C, Raulf F, Lottspeich, Schartl M, Thoenen H. Neurotrophin-6 is a new member of the nevre growth factor family. Nature. 1994; 372:2662
30. Hallböök F, Ibanez CF, Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron. 1991; 6:845-858.
31. Hallböök F. Evolution of the vertebrate neurotrophin and Trk receptor gene families. Curr Opin Neurobiol. 1999; 9:616-621.
32. Hofer M, Pagliusi SR, Hohn A, Leibrock J, Barde YA. Regional distribution of brainderived neurotrophic factor mRNA in the adult mouse brain. EMBO J. 1990; 9:245924
33. Hohn A, Leibrock J, Bailey K, Barde YA. Identification and characterization of a novel member of the nerve growth factor/brainderived neurotrophic factor family. Nature. 1990; 344:339-341.
34. Horch HW, Kruttgen A, Portbury SD, Katz LC. Destabilization of cortical dendrites and spines by BDNF. Neuron. 1999; 23:353-364.
35. Horch HW, Katz LC. BDNF release from single cells elicits local dendritic growth in nearby neurons. Nat Neurosci. 2002; 5:1177-1184.
36. Huang EJ, Reichardt L. Neurotrophins: Roles in Neuronal Development and Function. Annu Rev Neurosci. 2001; 24:677-736.
37. Hynes MA, Poulsen K, Armanini M, Berkemeier L, Phillips H, Rosenthal A. Neurotrophin4/5 is a survival factor for embryonic midbrain dopaminergic neurons in enriched cultures. J Neurosci Res. 1994; 37:144-154.
38. Ibanez CF, Ernfors P, Timmusk T, Ip NY, Arenas E, Yancopoulos GD, Persson H. Neurotrophin-4 is a target-derived neurotrophic factor for neurons of the trigeminal ganglion. Development. 1993; 117:1345-1353.
39. Ip NY, Ibanez CF, Nye SH, McClain J, Jones PF, Gies DR, Belluscio L, Le Beau MM, Espinosa R, Squinto SP. Mammalian neurotrophin-4: structure, chromosomal localization, tissue distribution, and receptor specificity. Proc Natl Acad Sci. 1992; 89:3060-3064.
40. Isackson PJ, Towner MD, Huntsman MM. Comparison of mammalian, chicken and xenopus brain-derived neurotrophic factor coding sequences. FEBS Lett. 1991; 285:2602
41. Kannan Y, Ushio H, Koyama H, Okada M, Oikawa M, Yoshihara T, Kaneko M, Matsuda H. 2.5S nerve growth factor enhances survival, phagocytosis, and superoxide production of murine neutrophils. Blood. 1991; 77:1320-1325.
42. Kaplan DR, Miller FD. Signal transduction by the neurotrophin receptors. Curr Opin Cell Biol. 1997; 9:213-221.
43. Kelly JA, Singer E, Osslund TD, Yeates TO. Crystallization and preliminary structural studies of neurotrophin-3. Protein Sci. 1994; 3(6):982-983.
44. Kennedy A, Wellmer A, Facer P, Saldanha G, Kopelman P, Lindsay RM, Anand P. Neurotrophin-3 is increased in skin in human diabetic neuropathy. J Neurol Neurosurg Psychiatry. 1998; 65:393-395.
45. Kerschensteiner M, Gallmeier E, Behrens L. Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med. 1999; 189(5):865-870.
46. Klesse LJ, Parada LF. Trks: Signal transduction and intracellular pathways. Microsc Res Tech. 1999; 45:210-216.
47. Koh S, Loy R. Age-related loss of nerve growth factor sensitivity in rat basal forebrain neurons. Brain Res. 1988; 440:396-401.
48. Koliatsos VE, Cayouettes MH, Berkeneier LR, Clatterbuck RE, Price DL, Rosenthal E. Neurotrophin 4/5 is a trophic factor for mammalian facial motor neurons. Proc Nadl Acad Sci. 1994; 91:3304-3308.
49. 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
50. La-Sala A, Corinti S, Federici M, Saragovi HU, Girolomoni G. Ligand activation of nerve growth factor receptor TrkA protects monocytes from apoptosis. J Leukoc Biol. 2000; 68:104-110.
51. Leibrock J, Lottspeich F, Hohn A, Hofer M, Hengerer B, Masiakowski P, Thoenen H, Barde, YA. Molecular cloning and expression of brain-derived neurotrophic factor. 1989; Nature. 341:149-152.
52. Leon A, Buiuani A, Dal Toso R, Fabris M, Romanello S, Aloeo A, Levi-Montalcini R. Mast cells synthesize, store, and release nerve growth factor. J Neurobiol. 1994; 91:373937
53. 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; 116:321-361.
54. Levi-Montalcini R, Angeletti PU. The nerve growth factor. Physiol Rev. 1968; 48:534-569.
55. Li X, Franz J, Lottspeich F, Götz R. Recombinant fish neurotrophin-6 is a heparin-binding glycoprotein implications for a role in axonal guidance. J Biochem. 1997; 324:461-466.
56. Lindholm D, Carroll P, Tzimagiogis G, Thoenen H. Autocrine-paracrine regulation of hippocampal neuron survival by IGF-1 and the neurotrophins BDNF, NT-3 and NT-4. Eur J Neurosci. 1996; 8:1452-1460.
57. Lingor P, Unsicker K, Krieglstein K. GDNF and NT-4 protect midbrain dopaminergic neurons from toxic damage by iron and nitric oxide. Exp Neurol. 2000; 163:55-62.
58. Lommatzsch M, Braun A, Mannsfeldt A, Botchkarev VA, Botchkareva NV, Paus R, Fischer A, Lewin GR, Renz H. Abundant production of brain-derived neurotrophic factor by adult visceral epithelia. Implications for paracrine and target-derived Neurotrophic functions. J Pathol. 1999; 155:1183-1193.
59. Lommatzsch M, Zingler D, Schuhbaeck K, Schloetcke K, Zingler C, Schuff-Werner P, Virchow JC. The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging. 2005; 26:115-123.
60. Longo FM, Massa SM. Small-molecule modulation of neurotrophin receptors: a strategy for the treatment of neurological disease. Nat Rev Drug Discov. 12:507-525. Lu B, Yokoyama M, Dreyfus CF, Black IB. NGF gene expression in actively growing brain glia. J Neurosci. 1991; 11:318-326.
61. Maisonpierre PC, Belluscio L, Friedman B, Alderson, RF, Wiegand, SJ, Furth ME. NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression. Neuron. 1990 a; 5:501-509.
62. Maisonpierre PC, Belluscio L, Squinto S, Ip NY, Furth ME, Lindsay RM, Yancopoulos GD. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 1990 b; 247(4949):1446-1451.
63. Mamidipudi V, Wooten MW. Dual role for p75(NTR) signaling in survival and cell death: Can intracellular mediators provide an explanation? J Neurosci Res. 2002; 68:3733
64. Manni L, Rocco ML, Bianchi, Soligo, Guaragna M, Barbaro, Aloe L. Nerve growth factor: basic studies and possible therapeutic applications. Growth Factors. 2013; 31(4):115-122.
65. Matthews VB, Astrom MB, Chan MH, Bruce CR, Krabbe KS, Prelovsek O, Akerstro¨m T, Yfanti C, Broholm C, Mortensen OH, Penkowa M, Hojman P, Zankari A, Watt MJ, Bruunsgaard H, Pedersen BK, Febbraio MA. Brain derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP activated protein kinase. Diabetologia. 2009; 52:140914
66. McAllister AK, Lo DC, Katz LC. Neurothrophins regulate dendritic growth in developing visual cortex. Neuron. 1995; 15:791-803.
67. Mowla SJ, Pareek S, Farhad HF, Petrecca K, Fawcet JP, Seidah NG, Morris SJ, Sossin WS, Murphy RA. Differential Sorting of Nerve Growth Factor and Brain-Derived Neurotrophic Factor in Hippocampal Neurons. J Neurosci. 1999; 19(6):2069-2080.
68. Mowla SJ, Farhadi HF, Pareek S, Atwal JK, Morris SJ, Seidah NG, Murphy RA. Biosynthesis and post-translational processing of the precursor to brain-derived neurotrophic factor. J Biol Chem. 2001; 276:12660-12666.
69. Murer MG, Yan Q, Raisman-Vozari R. Brain derived neurotrophic factor in the control human brain, and in Alzheimer's disease and Parkinson's disease. Prog Neurobiol. 2001; 63:71-124.
70. Nilsson AS, Fainzilber M, Falck P, Ibanez CF. Neurotrophin-7 a novel member of the neurotrophin family from the zebrafish. FEBS Letters. 1998; 424:285-290.
71. Otten U, Ehrhard P, Peck R. Nerve growth factor induces growth and differentiation of human B lymphocytes. Proc Natl Acad Sci. 1989; 86:10059-10063.
72. Park KI, Himes BT, Stieg PE, Tessler A, Fischer I, Snyder EY. Neural stem cells may be uniquely suited for combined gene therapy and cell replacement: Evidence from engraftment of Neurotrophin-3-expressing stem cells in hypoxic-ischemic brain injury. Exp Neurol. 2006; 199:179-190.
73. Patapoutian A, Reichardt LF. Trk receptors: mediators of neurotrophin action. Curr Opin Neurobiol. 2001; 11:272-280.
74. Patterson SL, Abel T, Deuel TA, Martin KC, Rose JC, Kandel ER. Recombinant BDNF rescues deficits in basal synaptic transmission and hippocampal LTP in BDNF knockout mice. Neuron. 1996; 16:1137-1145.
75. Prakash YS, Thompson MA, Meuchel L, Pabelick CM, Mantilla CB, Zaidi S, Martin RJ. Neurotrophins in lung health and disease. Expert Rev Respir Med. 2010; 4(3):395-411.
76. Reichardt LF. Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci. 2006; 361:1545-1564.
77. Roux PP, Colicos MA, Barker PA, Kennedy TE. p75 neurotrophin receptor expression is induced in apoptotic neurons after seizure. J Neurosci. 1999; 19:6887-6896.
78. Rudge JS, Alderson RF, Pasnikowski E, McClain J, Ip NY, Lindsay RM. Expression of ciliary neurotrophic factor and the neurotrophins nerve growth factor, brainderived neurotrophic factor and neurotrophin-3 in cultured rat hippocampal astrocytes. Eur J Neurosci. 1992; 4:459-471.
79. Schmalbruch H, Rosenthal A. Neurotrophin-4/5 postpones the death of injured spinal motoneurons in newborn rats. Brain Res. 1995; 700:254-260.
80. Schober A, Wolf N, Huber K, Hertel R, Krieglstein K, Minichiello L, Kahane N, Widenfalk J, Kalcheim C, Olson L, Klein R, Lewin GR, Unsicker K. TrkB and neurotrophin-4 are important for development and maintenance of sympathetic preganglionic neurons innervating the adrenal medulla. J Neurosci. 1998; 18:7272-7284.
81. Shimazu K, Zhao M, Sakata K, Akbarian S, Bates B, Jaenisch R, Lu B. NT-3 facilitates hippocampal plasticity and learning and memory by regulating neurogenesis. Learn Mem. 2006; 13:307-315.
82. Spalding KL, Tan MM, Hendry IA, Harvey AR. Anterograde transport and trophic actions of BDNF and NT-4/5 in the developing rat visual system. Mol & Cell Neurosci. 2002; 19:485-500.
83. Stucky CL, Shin JB, Lewin GR. Neurotrophin-4: a survival factor for adult sensory neurons. Curr Biol. 2002; 12:1401-1404.
84. Suzuki S, Kiyosue K, Hazama S, Ogura A, Kashihara M,1 Hara T, Koshimizu H, Kojima M. Brain-derived neurotrophic Factor regulates cholesterol metabolism for synapse development. J Neurosci. 2007; 27(24):6417-6427.
85. Tapia-Arancibia L, Rage F, Givalois L. Arancibia S. Physiology of BDNF: focus on hypothalamic function. Front Neuroendocrinol. 2004; 25(2):77-107.
86. Timmusk T, Belluardo N, Metsis M, Persson H. Widespread and developmentally regulated expression of neurotrophin-4 mRNA in rat brain and peripheral tissues. Eur J Neurosci. 1993a; 5(6):605-613.
87. Timmusk T, Palm K, Metsis M, Reintam T, Paalme V, Saarma M. Multiple promoters direct tissue specific expression of the rat BDNF gene. Neuron 1993b; 10:475-489.
88. Tokunaga Y, Kira R, Takahata Y, Gondo K, Mizuno Y, Aoki T, Hara T. Neurotrophin-4 and glial cell line-derived neurotrophic factor in cerebrospinal fluid from meningitis/ encephalitis patients. Pediatr Neurol. 2002; 27:102-105.
89. Vega JA, Suarez OG, Hannestad J, Perez MP, Germana A. Neurotrophins and the immune system. J Anat. 2003; 203:1-19.
90. Wetmore C, Cao YH, Pettersson RF, Olson L. Brain-derived neurotrophic factor: subcellular compartmentalization and interneuronal transfer as visualized with anti-peptide antibodies. Proc Natl Acad Sci. 1991; 88:9843-9847.
91. Woo NH, Lu B. BDNF in Synaptic Plasticity and Memory. National Institutes of Health, Bethesda, MD, USA by Elsevier Ltd. 2009; pp: 135-1 http://pdf.document3.com/bdnf-in-synapticplasticity-and-memory-the-university-ofsouth-download-w1253/; Erişim tarihi; 13
92. Yamamoto H, Gurney ME. Human Platelets Contain Brain-Derived Neurotrophic Factor. J Neurosci. 1990; 10(11):3469-3478.
93. Yamamoto M, Sobue G, Yamamoto K, Terao S, Mitsuma T. Expression of mRNAs for neurotrophic factors (NGF, BDNF, NT-3, and GDNF) and their receptors (p75 NGFR , trkA, trkB, and trkC) in the adult human peripheral nervous system and nonneural tissues. Neurochem Res. 1996; 21:929-938.
94. Yano H, Chao MV. Neurotrophin receptor structure and interactions. Pharm Acta Helv. 2000; 74:253-260.
95. Yoo YM, Kim YJ, Lee U, Paik DJ, Yoo HT, Park CW, Kim YB, Lee SG, Kim WK, Yoo CJ. Neurotrophic Factor in the Treatment of Parkinson Disease. Neurosurg Focus. 2003; 15(1):1-5.
96. Zheng JL, Stewart RR, Gael WQ. Neurotrophin4/5 Enhances Survival of Cultured Spiral Ganglion Neurons and Protects Them from Cisplatin Neurotoxicity. J Neurosci. 1995; 15(7):5079-5087.