Skip to main content
SpringerLink
Log in

Neurotrophic Factors

  • Chapter
Transgenic Models in Pharmacology

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 159))

  • 126 Accesses

Abstract

Since the discovery of nerve growth factor (NGF) and original observations that limiting quantities of this protein regulate survival of distinct populations of neurons during development, a broad variety of neurotrophic factors has been identified. These factors are members of several gene families and promote their effects though specific membrane receptors which either include transmembrane receptor tyrosine kinases or classical cytokine receptor subunits such as gp130. Neurotrophic factors do not only regulate neuronal survival but also neural differentiation, neurite outgrowth, synapse formation, transmitter synthesis and release. Additional functions in other organs than the nervous systems have also been identified. Mouse models in which the genes for these factors are specifically deleted have played an important role in our present understanding of the physiological function of these molecules. These findings are summarized and discussed in this review.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adler, R., Landa, K.B., Manthorpe, M., and Varon, S. (1979) Cholinergic neurotrophic factors: intraocular distribution of trophic activity for ciliary neurons. Science 204, 1434–1436

    Article  PubMed  CAS  Google Scholar 

  • Airaksinen, M.S. and Saarma, M. (2002) The GDNF family: signalling, biological functions and therapeutic value. Nat.Rev.Neurosci. 3, 383–394

    Article  PubMed  CAS  Google Scholar 

  • Aletta, J.M. (1994) Differential effect of NGF and EGF on ERK in neuronally differentiated PC 12 cells. Neuroreport 5, 2090–2092

    Article  PubMed  CAS  Google Scholar 

  • Alexander, W.S., Rakar, S., Robb, L., Farley, A., Willson, T.A., Zhang, J.G., Hartley, L., Kikuchi, Y., Kojima, T., Nomura, H., Hasegawa, M., Maeda, M., Fabri, L., Jachno, K., Nash, A., Metcalf, D., Nicola, N.A., and Hilton, D.J. (1999) Suckling defect in mice lacking the soluble haemopoietin receptor NR6. Curr.Biol. 9, 605–608

    Article  PubMed  CAS  Google Scholar 

  • Baloh, R.H., Enomoto, H., Johnson, E.M., Jr., and Milbrandt, J. (2000) The GDNF family ligands and recept. Curr.Opin.Neurobiol. 10, 103–110

    Article  PubMed  CAS  Google Scholar 

  • Bar-Sagi, D. and Feramisco, J.R. (1985) Microinjection of the ras oncogene protein into PC 12 cells induces morphological differentiation. Cell 42, 841–848

    Article  PubMed  CAS  Google Scholar 

  • Barbin, G., Manthorpe, M., and Varon, S. (1984) Purification of the chick eye ciliary neuronotrophic factor. J.Neurochem. 43, 1468–1478

    Article  PubMed  CAS  Google Scholar 

  • Barde, Y.-A. (1990) The nerve growth factor family. Progress in Growth Factor Research 2, 237–248

    Article  PubMed  CAS  Google Scholar 

  • Barres, B.A., Jacobson, M.D., Schmid, R., Sendtner, M., and Raff, M.C. (1993) Does oligodendrocyte survival depend on axons? Current Biology 3, 489–497

    Article  PubMed  CAS  Google Scholar 

  • Baxter, R.M., Cohen, P., Obermeier, A., Ullrich, A., Downes, C.P., and Doza, Y.N. (1995) Phosphotyrosine residues in the nerve-growth-factor receptor (Trk-A) Their role in the activation of inositolphospholipid metabolism and protein kinase cascades in phaeochromocytoma (PC12) cells. Eur.J.Biochem. 234, 84–91

    Article  PubMed  CAS  Google Scholar 

  • Berkemeier, L.R., Winslow, J.W., Kaplan, D.R., Nikolics, K., Goeddel, D.V., and Rosenthal, A. (1991) Neurotrophin-5: A novel neurotrophic factor that activates trk and trkB. Neuron 7, 857–866

    Article  PubMed  CAS  Google Scholar 

  • Blondet, B., Hantaz Ambroise, D., Ait Ikhlef, A., Cambier, D., Murawsky, M., and Rieger, F. (1995) Astrocytosis in wobbler mouse spinal cord involves a population of astrocytes which is glutamine synthetase-negative. Neurosci Lett 183, 179–182

    Article  PubMed  CAS  Google Scholar 

  • Boemel, H., Xie, G., Rossoll, W., Wiese, S., Jablonka, S., Boehm, T., and Sendtner, M. (2002) Missense mutation in the tubulin-specific chaperone E (Tbce) gene in the mouse mutant progressive motor neuronopathy, a model of human motoneuron disease. Journal of Cell Biology 159, 563–569

    Article  CAS  Google Scholar 

  • Borasio, G.D., Markus, A., Wittinghofer, A., Barde, Y.A., and Heumann, R. (1993) Involvement of ras p21 in neurotrophin-induced response of sensory, but not sympathetic neurons. Journal of Cell Biology 121, 665–672

    Article  PubMed  CAS  Google Scholar 

  • Bothwell, M. (1996) p75NTR: a receptor after all. Science 272, 506–507

    Article  PubMed  CAS  Google Scholar 

  • Brady, R., Zaidi, S.I., Mayer, C., and Katz, D.M. (1999) BDNF is a target-derived survival factor for arterial baroreceptor and chemoafferent primary sensory neurons. J.Neurosci. 19, 2131–2142

    PubMed  CAS  Google Scholar 

  • Bronson, R.T., Lake, B.D., Cook, S., Taylor, S., and Davisson, M.T. (1993) Motor neuron degeneration of mice is a model of neuronal ceroid lipofuscinosis (Batten’s disease) Ann.Neurol. 33, 381–385

    Article  PubMed  CAS  Google Scholar 

  • Brunet, A., Bonni, A., Zigmond, M.J., Lin, M.Z., Juo, P., Hu, L.S., Anderson, M.J., Arden, K.C., Blenis, J., and Greenberg, M.E. (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96, 857–868

    Article  PubMed  CAS  Google Scholar 

  • Cardone, M.H., Roy, N., Stennicke, H.R., Salvesen, G.S., Franke, T.F., Stanbridge, E., Frisch, S., and Reed, J.C. (1998) Regulation of cell death protease caspase-9 by phosphorylation. SCIENCE 282, 1318–1321

    Article  PubMed  CAS  Google Scholar 

  • Carter, B.D., Zirrgiebel, U., and Barde, Y.A. (1995) Differential regulation of p21ras activation in neurons by nerve growth factor and brain-derived neurotrophic factor. J Biol Chem 270, 21751–21757

    Article  PubMed  CAS  Google Scholar 

  • Cattaneo, E. and Pelicci, P.G. (1998) Emerging roles for SH2/PTB-containing Shc adaptor proteins in the developing mammalian brain. Trends Neurosci. 21, 476–481

    Article  PubMed  CAS  Google Scholar 

  • Conover, J.C., Erickson, J.T., Katz, D.M., Bianchi, L.M., Poueymirou, W.T., McClain, J., Pan, L., Helgren, M., Ip, N.Y., Boland, P., Friedman, B., Wiegand, S., Vejsada, R., Kato, A.C., DeChiara, T.M., and Yancopoulos, G.D. (1995) Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4. Nature 375, 235–238

    Article  PubMed  CAS  Google Scholar 

  • Conti, L., De Fraja, C., Gulisano, M., Migliaccio, E., Govoni, S., and Cattaneo, E. (1997) Expression and activation of SH2/PTB-containing ShcA adaptor protein reflects the pattern of neurogenesis in the mammalian brain. Proc.Natl.Acad.Sci.U.S.A 94, 8185–8190

    Article  PubMed  CAS  Google Scholar 

  • Crowley, C., Spencer, S.D., Nishimura, M.C., Chen, K.S., Pitts-Meek, S., Armanini, M.P., Ling, L.H., McMahon, S.B., Shelton, D.L., Levinson, A.D., and Phillips, H.S. (1994) Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons. Cell 76, 1001–1011

    Article  PubMed  CAS  Google Scholar 

  • Datta, S.R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y., and Greenberg, M.E. (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91, 231–241

    Article  PubMed  CAS  Google Scholar 

  • Davis, S., Aldrich, T.H., Ip, N.Y., Stahl, N., Scherer, S., Farruggella, T., Distefano, P.S., Curtis, R., Panayotatos, N., Gascan, H., Chevalier, S., and Yancopoulos, G.D. (1993) Released form of cntf receptor-alpha component as a soluble mediator of cntf responses. SCIENCE 259, 1736–1739

    Article  PubMed  CAS  Google Scholar 

  • Dechant, G. and Barde, Y.A. (1997) Signalling through the neurotrophin receptor p75NTR. Current Opinion in Neurobiology 7, 413–418

    Article  PubMed  CAS  Google Scholar 

  • DeChiara, T.M., Vejsada, R., Poueymirou, W.T., Acheson, A., Suri, C., Conover, J.C., Friedman, B., McClain, J., Pan, L., Stahl, N., Ip, N.Y., Kato, A., and Yancopoulos, G.D. (1995) Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor neuron deficits at birth. Cell 83, 313–322

    Article  PubMed  CAS  Google Scholar 

  • Deckwerth, T.L., Easton, R.M., Knudson, C.M., Korsmeyer, S.J., and Johnson, E.M., Jr. (1998) Placement of the BCL2 family member BAX in the death pathway of sympathetic neurons activated by trophic factor deprivation. Exp.Neurol. 152, 150–162

    Article  PubMed  CAS  Google Scholar 

  • Deshmukh, M. and Johnson, E.M., Jr. (1998) Evidence of a novel event during neuronal death: development of competence-to-die in response to cytoplasmic cytochrome c]. Neuron 21, 695–705

    Article  PubMed  CAS  Google Scholar 

  • Deveraux, Q.L., Roy, N., Stennicke, H.R., Van Arsdale, T., Zhou, Q., Srinivasula, S.M., Alnemri, E.S., Salvesen, G.S., and Reed, J.C. (1998) IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J. 17, 2215–2223

    Article  PubMed  CAS  Google Scholar 

  • Devereaux, Q.L., Takahashi, R., Salvesen, G.S., and Reed, J.C. (1997) X-linked IAP is a direct inhibitor of cell-death proteases. 1995 Nature 388, 300–304

    CAS  Google Scholar 

  • Digby, M.R., Kimpton, W.G., York, J.J., Connick, T.E., and Lowenthal, J.W. (1996) ITA, a vertebrate homologue of IAP that is expressed in T lymphocytes. DNA Cell Biol. 15, 981–988

    Article  PubMed  CAS  Google Scholar 

  • Dubois-Dauphin, M., Frankowski, H., Tsujimoto, Y., Huarte, J., and Martinou, J.-C. (1994) Neonatal motoneurons overexpressing the bcl-2 protooncogene in transgenic mice are protected from axotomy-induced cell death. Proceedings of the national academy of science USA 91, 3309–3313

    Article  CAS  Google Scholar 

  • Dudek, H., Datta, S.R., Franke, T.F., Birnbaum, M.J., Yao, R., Cooper, G.M., Segal, R.A., Kaplan, D.R., and Greenberg, M.E. (1997) Regulation of neuronal survival by the serine-threonine protein kinase Akt. SCIENCE 275, 661–665

    Article  PubMed  CAS  Google Scholar 

  • Durbec, P., Marcos Gutierrez, C.V., Kilkenny, C., Grigoriou, M., Wartiowaara, K., Suvanto, P., Smith, D., Ponder, B., Costantini, F., Saarma, M., Sariola, H., and Pachnis, V. (1996) GDNF signalling through the Ret receptor tyrosine kinase. Nature 381, 789–793

    Article  PubMed  CAS  Google Scholar 

  • Eide, F.F., Lowenstein, D.H., and Reichardt, L.F. (1993) Neurotrophins and their receptors-Current concepts and implications for neurologic disease. Exp.Neurol. 121, 200–214

    Article  PubMed  CAS  Google Scholar 

  • Elson, G.C., Lelievre, E., Guillet, C., Chevalier, S., Plun-Favreau, H., Froger, J., Suard, I., de Coignac, A.B., Delneste, Y., Bonnefoy, J.Y., Gauchat, J.F., and Gascan, H. (2000) CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex. Nat.Neurosci. 3, 867–872

    Article  PubMed  CAS  Google Scholar 

  • Enomoto, H., Araki, T., Jackman, A., Heuckeroth, R.O., Snider, W.D., Johnson, E.M., Jr., and Milbrandt, J. (1998) GFR alpha1-deficient mice have deficits in the enteric nervous system and kidneys. Neuron 21, 317–324

    Article  PubMed  CAS  Google Scholar 

  • Ernfors, P., Kucera, J., Lee, K.F., Loring, J., and Jaenisch, R. (1995) Studies on the physiological role of brain-derived neurotrophic factor and neurotrophin-3 in knockout mice. Int.J.Dev.Biol. 39, 799–807

    PubMed  CAS  Google Scholar 

  • Ernfors, P., Lee, K.-F., Kucera, J., and Jaenisch, R. (1994) Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents. Cell 77, 503–512

    Article  PubMed  CAS  Google Scholar 

  • Ernfors, P. and Persson, H. (1991) Developmentally regulated expression of NDNF/NT-3 mRNA in rat spinal cord motoneurons and expression of BDNF mRNA in embryonic dorsal root ganglion. European Journal of Neuroscience 3, 953–961

    Article  PubMed  Google Scholar 

  • Escary, J.-L., Perreau, J., Duménil, D., Ezine, S., and Brulet, P. (1993) Leukaemia inhibitory factor is necessary for maintenance of haematopoietic stem cells and thymocyte stimulation. Nature 363, 361–364

    Article  PubMed  CAS  Google Scholar 

  • Fantuzzi, G., Benigni, F., Sironi, M., Conni, M., Carelli, M., Cantoni, L., Shapiro, L., Dinarello, C.A., Sipe, J.D., and Ghezzi, P. (1995) Ciliary neurotrophic factor (CNTF) induces serum amyloid A, hypoglycaemia and anorexia, and potentiates IL-1 induced corticosterone and IL-6 production in mice. Cytokine. 7, 150–156

    Article  PubMed  CAS  Google Scholar 

  • Finkbeiner, S., Tavazoie, S.F., Maloratsky, A., Jacobs, K.M., Harris, K.M., and Greenberg, M.E. (1997) CREB: a major mediator of neuronal neurotrophin responses. Neuron 19, 1031–1047

    Article  PubMed  CAS  Google Scholar 

  • Frade, J.M., Rodriguez Tebar, A., and Barde, Y.A. (1996) Induction of cell death by endogenous nerve growth factor through its p75 receptor. Development 383, 166–168

    CAS  Google Scholar 

  • Funakoshi, H., Belluasdo, N., Arenas, E., Yamamoto, Y., Casabona, A., Persson, H., and Ibanez, C.F. (1995) Muscle-derived Neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons. SCIENCE 268, 1495–1499

    Article  PubMed  CAS  Google Scholar 

  • Gearing, D.P., Comeau, M.R., Friend, D.J., Gimpel, S.D., Thut, C.J., McGourty, J., Brasher, K.K., King, J.A., Gillis, S., Mosley, B., and et al (1992) The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor. SCIENCE 255, 1434–1437

    Article  PubMed  CAS  Google Scholar 

  • Gearing, D.P., Thut, C.J., VandeBos, T., Gimpel, S.D., Delaney, P.B., King, J., Price, V., Cosman, D., and Beckmann, M.P. (1991) Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130. EMBO J. 10, 2839–2848

    PubMed  CAS  Google Scholar 

  • Giess, R., Beck, M., Goetz, R., Nitsch, R.M., Toyka, K.V., and Sendtner, M. (2000a) Potential role of LIF as a modifier gene in the pathogenesis of amyotrophic lateral sclerosis. Neurology 54, 1003–1005

    Article  PubMed  CAS  Google Scholar 

  • Giess, R., Beck, M., Goetz, R., Nitsch, R.M., Toyka, K.V., and Sendtner, M. (2000b) Potential role of LIF as a modifier gene in the pathogenesis of amyotrophic lateral sclerosis Neurology 54, 1003–1005

    Article  PubMed  CAS  Google Scholar 

  • Giess, R., Holtmann, B., Braga, M., Grimm, T., Muller-Myhsok, B., Toyka, K.V., and Sendtner, M. (2002a) Early onset of severe familial amyotrophic lateral sclerosis with a SOD-1 mutation: potential impact of CNTF as a candidate modifier gene. Am.J.-Hum.Genet. 70, 1277–1286

    Article  PubMed  CAS  Google Scholar 

  • Giess, R., Maurer, M., Linker, R., Gold, R., Warmuth-Metz, M., Toyka, K.V., Sendtner, M., and Rieckmann, P. (2002b) Association of a null mutation in the CNTF gene with early onset of multiple sclerosis. Arch.Neurol. 59, 407–409

    Article  PubMed  Google Scholar 

  • Ginty, D.D. and Segal, R.A. (2002) Retrograde neurotrophin signaling: Trk-ing along the axon. Curr.Opin.Neurobiol. 12, 268–274

    Article  PubMed  CAS  Google Scholar 

  • Gravel, C, Götz, R., Lorrain, A., and Sendtner, M. (1997) Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to longterm survival of axotomized motoneurons. Nature Medicine 3, 765–770

    Article  PubMed  CAS  Google Scholar 

  • Greene, L.A. and Kaplan, D.R. (1995) Early events in neurotrophin signalling via Trk and p75 receptors. Curr.Opin.Neurobiol. 5, 579–587

    Article  PubMed  CAS  Google Scholar 

  • Grewal, S.S., Horgan, A.M., York, R.D., Withers, G.S., Banker, G.A., and Stork, P.J. (2000) Neuronal Calcium Activates a Rap1 and B-Raf Signaling Pathway via the Cyclic Adenosine Monophosphate-dependent Protein Kinase. Journal of Biological Chemistry 275, 3722–3728

    Article  PubMed  CAS  Google Scholar 

  • Griesbeck, O., Parsadanian, A.Sh., Sendtner, M., and Thoenen, H. (1995) Expression of neurotrophins in skeletal muscle: Quantitative comparison and significance for motoneuron survival and maintenance of function. J.Neurosci.Res. 42, 21–33

    Article  PubMed  CAS  Google Scholar 

  • Hallböök, F., Ibáñez, CF., and Persson, H. (1991) Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron 6, 845–858

    Article  PubMed  Google Scholar 

  • Hamburger, V. (1934) The effects of wing bud extirpation on the development of the central nervous system in chick embryos. J.Exp.Zool. 68, 449–494

    Article  Google Scholar 

  • Hamburger, V. (1958) Regression versus peripheral control of differentiation in motor hyperplasia. Am.J.Anat. 102, 365–410

    Article  PubMed  CAS  Google Scholar 

  • Hartikka, J. and Hefti, F. (1988) Comparison of nerve growth factor’s effects on development of septum, striatum, and nucleus basalis cholinergic neurons in vitro. J.Neurosci.Res. 21, 352–364

    Article  PubMed  CAS  Google Scholar 

  • Helgren, M.E., Friedman, B., Kennedy, M., Mullholland, K., Messer, A., Wong, V., and Lindsay, R.M. Ciliary neurotrophic factor (CNTF) delays motor impairments in the mnd mouse, a genetic model of motor neuron disease. Neurosci.Abstr. 267.11, 618. 1992

    Google Scholar 

  • Henderson, C.E., Camu, W., Mettling, C., Gouin, A., Poulsen, K., Karihaloo, M., Rullamas, J., Evans, T., McMahon, S.B., Armanini, M.P., Berkemeier, L., Phillips, H.S., and Rosenthal, A. (1993) Neurotrophins promote motor neuron survival and are present in embryonic limb bud. Nature 363, 266–270

    Article  PubMed  CAS  Google Scholar 

  • Henderson, C.E., Phillips, H.S., Pollock, R.A., Davies, A.M., Lemeulle, C., Armanini, M., Simpson, L.C., Moffet, B., Vandlen, R.A., Koliatsos, V.E., and et al (1994) GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle. SCIENCE 266, 1062–1064

    Article  PubMed  CAS  Google Scholar 

  • Heuckeroth, R.O., Enomoto, H., Grider, J.R., Golden, J.P., Hanke, J.A., Jackman, A., Molliver, D.C., Bardgett, M.E., Snider, W.D., Johnson, E.M., Jr., and Milbrandt, J. (1999) Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons. Neuron 22, 253–263

    Article  PubMed  CAS  Google Scholar 

  • Hohn, A., Leibrock, J., Bailey, K., and Barde, Y.-A. (1990) Identification and characterzation of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. Nature 344, 339–341

    Article  PubMed  CAS  Google Scholar 

  • Holliday,M. and Hamburger, V. (1975) Reduction of the naturally occuring motor neuron loss by enlargement of the periphery. J.Comp.Neurol. 170, 311–320

    Article  Google Scholar 

  • Hughes, R.A., Sendtner, M., and Thoenen, H. (1993) Members of several gene families influence survival of rat motoneurons in vitro and in vivo. J.Neurosci.Res. 36 (6), 663–671

    Article  PubMed  CAS  Google Scholar 

  • Jing, S., Wen, D., Yu, Y., Holst, P.L., Luo, Y., Fang, M., Tamir, R., Antonio, L., Hu, Z., Cupples, R., Louis, J.C., Hu, S., Altrock, B.W., and Fox, G.M. (1996) GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF. Cell 85, 1113–1124

    Article  PubMed  CAS  Google Scholar 

  • Kaplan, D.R. and Miller, F.D. (2000) Neurotrophin signal transduction in the nervous system. Curr.Opin.Neurobiol. 10, 381–391

    Article  PubMed  CAS  Google Scholar 

  • Kerkhoff, H., Troost, D., Louwerse, E.S., Van Dijk, M., Veldman, H., and Jennekens, F.G.I. (1993) Inflammatory cells in the peripheral nervous system in motor neuron disease. Acta Neuropathol.(Berl.) 85, 560–565

    Article  CAS  Google Scholar 

  • Klein, R., Silos-Santiago,I., Smeyne, R.J., Lira, S.A., Brambilla, R., Bryant, S., Zhang, L., Snider, W.D., and Barbacid, M. (1994) Disruption of the neurotrophin-3 receptor gene trkC eliminates Ia muscle afferents and results in abnormal movements. Nature 368, 249–251

    Article  PubMed  CAS  Google Scholar 

  • Klein, R., Smeyne, R.J., Wurst, W., Long, L.K., Auerbach, B.A., Joyner, A.L., and Barbacid, M. (1993) Targeted disruption of the trkB neurotrophin receptor results in nervous system lesions and neonatal death. Cell 75,113–122

    PubMed  CAS  Google Scholar 

  • Knudson, C.M., Tung, K.S., Tourtellotte, W.G., Brown, G.A., and Korsmeyer,S.J. (1995) Bax-deficient mice with lymphoid hyperplasia and male germ cell death. SCIENCE 270, 96–99

    Article  PubMed  CAS  Google Scholar 

  • Koliatsos, V.E., Shelton, D.L., Mobley, W.C., and Price, D.L. (1991) A novel group of nerve growth factor receptor-immunoreactive neurons in the ventral horn of the lumbar spinal cord. Brain Res. 541, 121–128

    Article  PubMed  CAS  Google Scholar 

  • Kucera, J., Ernfors, P., and Jaenisch, R. (1995) Reduction in the number of spinal motor neurons in neurotrophin-3-deficient mice. Neurosci. 69, 312–330

    Article  Google Scholar 

  • Lee, R., Kermani, P., Teng, K.K., and Hempstead, B.L. (2001) Regulation of cell survival by secreted proneurotrophins. SCIENCE 294, 1945–1948

    Article  PubMed  CAS  Google Scholar 

  • Leibrock, J., Lottspeich, F., Hohn, A., Hofer, M., Hengerer, B., Masiakowski, P., Thoenen, H., and Barde, Y.-A. (1989) Molecular cloning and expression of brain-derived neurotrophic factor. Nature 341, 149–152

    Article  PubMed  CAS  Google Scholar 

  • Levi-Montalcini, R. (1987) The nerve growth factor: thirty-five years later. EMBO J. 6, 1145–1154

    PubMed  CAS  Google Scholar 

  • Levi-Montalcini, R., Meyer, H., and Hamburger, V. (1954) In vitro experiments on the effects of mouse sarcomas 180 and 37 on the spinal and sympathetic ganglia of the chick embryo. Cancer Res. 14, 49–57

    PubMed  CAS  Google Scholar 

  • Li, M., Sendtner, M., and Smith, A. (1995a) Essential function of LIF receptor in motor neurons. Nature 378, 724–727

    Article  PubMed  CAS  Google Scholar 

  • Li, Y., Holtzman, D.M., Kromer, L.F., Kaplan, D.R., Chua-Couzens, J., Clary, D.O., Knusel, B., and Mobley, W.C. (1995b) Regulation of TrkA and ChAT expression in developing rat basal forebrain: evidence that both exogenous and endogenous NGF regulate differentiation of cholinergic neurons. J.Neurosci. 15, 2888–2905

    PubMed  CAS  Google Scholar 

  • Liebl, D.J., Tessarollo, L., Palko, M.E., and Parada, L.F. (1997) Absence of sensory neurons before target innervation in brain-derived neurotrophic factor-, neurotrophin 3-, and TrkC-deficient embryonic mice. J.Neurosci. 17, 9113–9121

    PubMed  CAS  Google Scholar 

  • Lin, L.-F., Mismer, D., Lile, J.D., Armes, L.G., Butler III, E.T., Vannice, J.L., and Collins, F. (1989) Purification, cloning, and expression of ciliary neurotrophic factor (CNTF) SCIENCE 246, 1023–1025

    Article  PubMed  CAS  Google Scholar 

  • Lin, L.-F.H., Doherty, D.H., Lile, J.D., Bektesh, S., and Collins, F. (1993) GDNF: A glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. SCIENCE 260, 1130–1132

    Article  PubMed  CAS  Google Scholar 

  • Liu, X., Ernfors, P., Wu, H., and Jaenisch, R. (1995) Sensory but not motor neuron deficits in mice lacking NT4 and BDNF. Nature 375, 238–240

    Article  PubMed  CAS  Google Scholar 

  • Liu, X. and Jaenisch, R. (2000) Severe peripheral sensory neuron loss and modest motor neuron reduction in mice with combined deficiency of brain-derived neurotrophic factor, neurotrophin 3 and neurotrophin 4/5. Dev.Dyn. 218, 94–101

    Article  PubMed  CAS  Google Scholar 

  • Lohof, A.M., Ip, N.Y., and Poo, M. (1993) Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. Nature 363, 350–353

    Article  PubMed  CAS  Google Scholar 

  • Lonze, B.E. and Ginty, D.D. (2002) Function and regulation of CREB family transcription factors in the nervous system. Neuron 35, 605–623

    Article  PubMed  CAS  Google Scholar 

  • Maisonpierre, P.C., Belluscio, L., Squinto, S.P., Ip, N.Y., Furth, M.E., Lindsay, R.M., and Yancopoulos, G.D. (1990) Neurotrophin-3: A neurotrophic factor related to NGF and BDNF. SCIENCE 247, 1446–1451

    Article  PubMed  CAS  Google Scholar 

  • Martin, N., Jaubert, J., Gounon, P., Salido, E., Haase, G., Szatanik, M., and Guenet, J.L. (2002) A missense mutation in Tbce causes progressive motor neuronopathy in mice. Nat.Genet. 32, 443–447

    Article  PubMed  CAS  Google Scholar 

  • Martinou, J.-C., Dubois-Dauphin, M., Staple, J.K., Rodriguez, I., Frankowski, H., Missotten, M., Albertini, P., Talabot, D., Catsicas, S., Pietra, C., and Huarte, J. (1994) Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13, 1017–1030

    Article  PubMed  CAS  Google Scholar 

  • Masu, Y., Wolf, E., Holtmann, B., Sendtner, M., Brem, G., and Thoenen, H. (1993) Disruption of the CNTF gene results in motor neuron degeneration. Nature 365, 27–32

    Article  PubMed  CAS  Google Scholar 

  • Maurer, M., Linker, R., Gold, R., Toyka, K.V., Sendtner, M., and Rieckmann, P. (2002) A Null Mutation in the CNTF Gene Is Not Associated With Early Onset of Multiple Sclerosis. Arch.Neurol. 59, 1974–1975

    Article  Google Scholar 

  • Metcalf, D. and Gearing, D.P. (1989) Fatal syndrome in mice engrafted with cells producing high levels of the leukemia inhibitory factor. Proc.Natl.Acad.Sci.U.S.A 86, 5948–5952

    Article  PubMed  CAS  Google Scholar 

  • Meyer, M., Matsuoka, I., Wetmore, C., Olson, L., and Thoenen, H. (1992) Enhanced synthesis of brain-derived neurotrophic factor in the lesioned peripheral nerve: Different mechanisms are responsible for the regulation of BDNF and NGF mRNA. Journal of Cell Biology 119, 45–54

    Article  PubMed  CAS  Google Scholar 

  • Michaelidis, T.M., Sendtner, M., Cooper, J.D., Airaksinen, M., Holtmann, B., Meyer, M., and Thoenen, H. (1996) Inactivation of the bcl-2 gene results in progressive degeneration of motoneurons, sensory and sympathetic neurons during early postnatal development. Neuron 17, 75–89

    Article  PubMed  CAS  Google Scholar 

  • Minichiello, L., Casagranda, F., Tatche, R.S., Stucky, C.L., Postigo, A., Lewin, G.R., Davies, A.M., and Klein, R. (1998) Point mutation in trkB causes loss of NT4-dependent neurons without major effects on diverse BDNF responses. Neuron 21, 335–345

    Article  PubMed  CAS  Google Scholar 

  • Minichiello, L. and Klein, R. (1996) TrkB and TrkC neurotrophin receptors cooperate in promoting survival of hippocampal and cerebellar granule neurons. Genes Dev. 10, 2849–2858

    Article  PubMed  CAS  Google Scholar 

  • Mitsumoto, H., Ikeda, K., Wong, V., Lindsay, R.M., and Cedarbaum, J.M. Recombinant human ciliary neurotrophic factor (rHCNTF) improves muscle strength in wobbler mouse motor neuron disease. Genetics and cell biology of the motor neurone. Third international Symposium on ALS/MND. T6. 1992

    Google Scholar 

  • Miyata, Y., Kashihara, Y., Homma, S., and Kuno, M. (1986) Effects of nerve growth factor on the survival and synaptic function of Ia sensory neurons axotomized in neonatal rats. J.Neurosci. 6, 2012–2018

    PubMed  CAS  Google Scholar 

  • Moore, M.W., Klein, R.D., Farinas, I., Sauer, H., Armanini, M., Phillips, H., Reichardt, L.F., Ryan, A.M., Carver Moore, K., and Rosenthal, A. (1996) Renal and neuronal abnormalities in mice lacking GDNF. Nature 382, 76–79

    Article  PubMed  CAS  Google Scholar 

  • Nakamura, T., Sanokawa, R., Sasaki, Y., Ayusawa, D., Oishi, M., and Mori, N. (1996) N-Shc:a neural-specific adapter molecule that mediates signaling from neurotrophin/ Trk to Ras/Mapk pathway. Oncogene 1111–1121

    Google Scholar 

  • Newmeyer, D.D. and Green, D.R. (1998) Surviving the cytochrome seas. Neuron 21, 653–655

    Article  PubMed  CAS  Google Scholar 

  • Nishino, J., Mochida, K., Ohfuji, Y., Shimazaki, T., Meno, C., Ohishi, S., Matsuda, Y., Fujii, H., Saijoh, Y., and Hamada, H. (1999) GFR alpha3, a component of the artemin receptor, is required for migration and survival of the superior cervical ganglion. Neuron 23, 725–736

    Article  PubMed  CAS  Google Scholar 

  • Obermeier, A., Bradshaw, R.A., Seedorf, K., Choidas, A., Schlessinger, J., and Ullrich, A. (1994) Neuronal differentiation signals are controlled by nerve growth factor receptor/Trk binding sites for SHC and PLCgamma. EMBO J. 13, 1585–1590

    PubMed  CAS  Google Scholar 

  • Obermeier, A., Lammers, R., Wiesmuller, K.H., Jung, G., Schlessinger, J., and Ullrich, A. (1993) Identification of Trk binding sites for SHC and phosphatidylinositol 3′-kinase and formation of a multimeric signaling complex. Journal of Biological Chemistry 268, 22963–22966

    PubMed  CAS  Google Scholar 

  • Oppenheim, R.W. (1991) Cell death during development of the nervous system. Annu.Rev.Neurosci. 14, 453–501

    Article  PubMed  CAS  Google Scholar 

  • Oppenheim, R.W., Houenou, L.J., Johnson, J.E., Lin, L.F., Li, L., Lo, A.C., Newsome, A.L., Prevette, D.M., and Wang, S. (1995) Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF. Nature 373, 344–346

    Article  PubMed  CAS  Google Scholar 

  • Oppenheim, R.W., Qin-Wei, Y., Prevette, D., and Yan, Q. (1992) Brain-derived neurotrophic factor rescues developing avian motoneurons from cell death. Nature 360, 755–757

    Article  PubMed  CAS  Google Scholar 

  • Oppenheim, R.W., Wiese, S., Prevette, D., Armanini, M., Wang, S., Houenou, L.J., Holtmann, B., Gotz, R., Pennica, D., and Sendtner, M. (2001) Cardiotrophin-1, a Muscle-Derived Cytokine, Is Required for the Survival of Subpopulations of Developing Motoneurons. J.Neurosci. 21, 1283–1291

    PubMed  CAS  Google Scholar 

  • Ozes, O.N., Mayo, L.D., Gustin, J.A., Pfeffer, S.R., Pfeffer, L.M., and Donner, D.B. (1999) NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature 401, 82–85

    Article  PubMed  CAS  Google Scholar 

  • Pennica, D., Shaw, K.J., Swanson, T.A., Moore, M.W., Shelton, D.L., Zioncheck, K.A., Rosenthal, A., Taga, T., Paoni, N.F., and Wood, W.I. (1995) Cardiotrophin-1. Biological activities and binding to the leukemia inhibitory factor receptor/gp130 signaling complex. Journal of Biological Chemistry 270, 10915–10922

    Article  PubMed  CAS  Google Scholar 

  • Pichel, J.G., Shen, L., Sheng, H.Z., Granholm, A.C., Drago, J., Grinberg, A., Lee, E.J., Huang, S.P., Saarma, M., Hoffer, B.J., Sariola, H., and Westphal, H. (1996) Defects in enteric innervation and kidney development in mice lacking GDNF. Nature 382, 73–76

    Article  PubMed  CAS  Google Scholar 

  • Pinon, L.G., Minichiello, L., Klein, R., and Davies, A.M. (1996) Timing of neuronal death in trkA, trkB and trkC mutant embryos reveals developmental changes in sensory neuron dependence on Trk signalling. Development 122, 3255–3261

    PubMed  CAS  Google Scholar 

  • Rabizadeh, S., Oh, J., Zhong, L., Yang, J., Bitler, C.M., Butcher, L.L., and Bredesen, D.E. (1993) Induction of apoptosis by the low-affinity NGF receptor. SCIENCE 261, 345–348

    Article  PubMed  CAS  Google Scholar 

  • Romashkova, J.A. and Makarov, S.S. (1999) NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling Nature 401, 86–90

    Article  PubMed  CAS  Google Scholar 

  • Rossi, J., Luukko, K., Poteryaev, D., Laurikainen, A., Sun, Y.F., Laakso, T., Eerikainen, S., Tuominen, R., Lakso, M., Rauvala, H., Arumae, U., Pasternack, M., Saarma, M., and Airaksinen, M.S. (1999) Retarded growth and deficits in the enteric and parasympathetic nervous system in mice lacking GFR alpha2, a functional neurturin receptor. Neuron 22, 243–252

    Article  PubMed  CAS  Google Scholar 

  • Ryffel, B. (1993) Pathology induced by leukemia inhibitory factor. Int.Rev.Exp.Pathol. 34 Pt B,69–72

    PubMed  Google Scholar 

  • Sanchez, M.P., Silos Santiago, I., Frisen, J., He, B., Lira, S.A., and Barbacid, M. (1996) Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382, 70–73

    Article  PubMed  CAS  Google Scholar 

  • Schnell, L., Schneider, R., Kolbeck, R., Barde, Y.-A., and Schwab, M.E. (1994) Neurotrophin-3 enhances sprouting of corticospinal tract during development and after spinal cord lesion. Nature 367, 170–173

    Article  PubMed  CAS  Google Scholar 

  • Schuchardt, A., D’Agati, V., Larsson-Blomberg, L., Costantini, F., and Pachnis, V. (1994) Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367, 380–383

    Article  PubMed  CAS  Google Scholar 

  • Seeburger, J.L., Tarras, S., Natter, H., and Springer, J.E. (1993) Spinal cord motoneurons express p75NGFR and p145trkB mRNA in amyotrophic lateral sclerosis. Brain Res. 621, 111–115

    Article  PubMed  CAS  Google Scholar 

  • Segal, R.A. and Greenberg, M.E. (1996) Intracellular signaling pathways activated by neurotrophic factors. Annu.Rev.Neurosci. 19, 463–489

    Article  PubMed  CAS  Google Scholar 

  • Sendtner, M., Götz, R., Holtmann, B., Escary, J.-L., Masu, Y, Carroll, P., Wolf, E., Brehm, G., Brulet, P., and Thoenen, H. (1996) Cryptic physiological trophic support of motoneurons by LIF disclosed by double gene targeting of CNTF and LIF. Current Biology 6, 686–694

    Article  PubMed  CAS  Google Scholar 

  • Sendtner, M., Holtmann, B., Kolbeck, R., Thoenen, H., and Barde, Y.-A. (1992a) Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section. Nature 360, 757–758

    Article  PubMed  CAS  Google Scholar 

  • Sendtner, M., Schmalbruch, H., Stöckli, K.A., Carroll, P., Kreutzberg, G.W, and Thoenen, H. (1992b) Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy. Nature 358, 502–504

    Article  PubMed  CAS  Google Scholar 

  • Shapiro, L., Zhang, X.-X., Rupp, R.G., Wolff, S.M., and Dinarello, C.A. (1993) Ciliary neurotrophic factor is an endogenous pyrogen. Proceedings of the national academy of science USA 90, 8614–8618

    Article  CAS  Google Scholar 

  • Silos-Santiago, I., Molliver, D.C., Ozaki, S., Smeyne, R.J., Fagan, A.M., Barbacid, M., and Snider, W.D. (1995) Non-TrkA-expressing small DRG neurons are lost in TrkA deficient mice. J.Neurosci. 15, 5929–5942

    PubMed  CAS  Google Scholar 

  • Slee, E.A., Harte, M.T., Kluck, R.M., Wolf, B.B., Casiano, C.A., Newmeyer, D.D., Wang, H.G., Reed, J.C., Nicholson, D.W., Alnemri, E.S., Green, D.R., and Martin, S.J. (1999) Ordering the Cytochrome c-initiated Caspase Cascade: Hierarchical Activation of Caspases-2,-3,-6,-7,-8, and-10 in a Caspase-9-dependent Manner. Journal of Cell Biology 144, 281–292

    Article  PubMed  CAS  Google Scholar 

  • Snider, W.D. (1994) Functions of the neurotrophins during nervous system development: What the knockouts are teaching us. Cell 77, 627–638

    Article  PubMed  Google Scholar 

  • Stahl, N. and Yancopoulos, G.D. (1994) The tripartite CNTF receptor complex: Activation and signaling involves components shared with other cytokines. J.Neurobiol. 25, 1454–1466

    Article  PubMed  CAS  Google Scholar 

  • Stennicke, H.R., Deveraux, Q.L., Humke, E.W., Reed, J.C., Dixit, V.M., and Salvesen, G.S. (1999) Caspase-9 can Be activated without proteolytic processing. Journal of Biological Chemistry 274, 8359–8362

    Article  PubMed  CAS  Google Scholar 

  • Stöckli, K.A., Lottspeich, F., Sendtner, M., Masiakowski, P., Carroll, P., Götz, R., Lindholm, D., and Thoenen, H. (1989) Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor. Nature 342, 920–923

    Article  PubMed  Google Scholar 

  • Stoeckel, K., Schwab, M., and Thoenen, H. (1975) Specificity of retrograde transport of nerve growth factor (NGF) in sensory neurons: a biochemical and morphological study. Brain Res. 81, 1–14

    Article  Google Scholar 

  • Strohmaier, C., Carter, B.D., Urfer, R., Barde, Y.A., and Dechant, G. (1996) A splice variant of the neurotrophin receptor trkB with increased specificity for brain-derived neurotrophic factor. EMBO J. 15, 3332–3337

    PubMed  CAS  Google Scholar 

  • Stucky, C.L., DeChiara, T., Lindsay, R.M., Yancopoulos, G.D., and Koltzenburg, M. (1998) Neurotrophin 4 is required for the survival of a subclass of hair follicle receptors. J.Neurosci. 18, 7040–7046

    PubMed  CAS  Google Scholar 

  • Takahashi, R., Yokoji, H., Misawa, H., Hayashi, M., Hu, J., and Deguchi, T. (1994) A null mutation in the human CNTF gene is not causally related to neurological diseases. Nature Genet. 7, 79–84

    Article  PubMed  CAS  Google Scholar 

  • Taraviras, S., Marcos-Gutierrez, C.V., Durbec, P., Jani, H., Grigoriou, M., Sukumaran, M., Wang, L.C., Hynes, M., Raisman, G., and Pachnis, V. (1999) Signalling by the RET receptor tyrosine kinase and its role in the development of the mammalian enteric nervous system. Development 126, 2785–2797

    PubMed  CAS  Google Scholar 

  • Thoenen, H. and Barde, Y.-A. (1980) Physiology of nerve growth factor. Physiol.Rev. 60, 1284–1335

    PubMed  CAS  Google Scholar 

  • Thoenen, H., Hughes, R.A., and Sendtner, M. (1993) Trophic support of motoneurons: Physiological, pathophysiological, and therapeutic implications. Exp.Neurol. 124, 47–55

    Article  PubMed  CAS  Google Scholar 

  • Tinhofer, I., Maly, K., Dietl, P., Hochholdinger, F., Mayr, S., Obermeier, A., and Grunicke, H.H. (1996) Differential Ca2+ signaling induced by activation of the epidermal growth factor and nerve growth factor receptors. Journal of Biological Chemistry 271, 30505–30509

    Article  PubMed  CAS  Google Scholar 

  • Traverse, S., Gomez, N., Paterson, H., Marshall, C., and Cohen, P. (1992) Sustained activation of the mitogen-activated protein (MAP) kinase cascade may be required for differentiation of PC12 cells. Comparison of the effects of nerve growth factor and epidermal growth factor. Biochem.J. 288, 351–355

    PubMed  CAS  Google Scholar 

  • Treanor, J.J., Goodman, L., de Sauvage, F., Stone, D.M., Poulsen, K.T., Beck, C.D., Gray, C., Armanini, M.P., Pollock, R.A., Hefti, F., Phillips, H.S., Goddard, A., Moore, M.W., Buj Bello, A., Davies, A.M., Asai, N., Takahashi, M., Vandlen, R., Henderson, C.E., and Rosenthal, A. (1996) Characterization of a multicomponent receptor for GDNF. Nature 382, 80–83

    Article  PubMed  CAS  Google Scholar 

  • Trupp, M., Arenas, E., Fainzilber, M., Nilsson, A.S., Sieber, B.A., Grigoriou, M., Kilkenny, C., Salazar Grueso,E., Pachnis, V., Arumae, U., Sariola, H., Saarma, M., and Ibanez, C.F. (1996) Functional receptor for GDNF encoded by the c-ret proto-oncogene. Nature 381, 785–788

    Article  PubMed  CAS  Google Scholar 

  • Van der Zee, C.E., Ross, G.M., Riopelle, R.J., and Hagg, T. (1996) Survival of cholinergic forebrain neurons in developing p75NGFR-deficient mice [retracted by Hagg T. In: Science 1999 Jul 16;285(5426):340]. SCIENCE 274, 1729–1732

    Article  PubMed  Google Scholar 

  • Vejsada, R., Sagot, Y., and Kato, A.C. (1994) BDNF-mediated rescue of axotomized motor neurones decreases with increasing dose. Neuroreport 5, 1889–1892

    Article  PubMed  CAS  Google Scholar 

  • Vejsada, R., Sagot, Y., and Kato, A.C. (1995) Quantitative comparison of the transient rescue effects of neurotrophic factors on axotomized motoneurons in vivo. Eur.J.Neurosci. 7, 108–115

    Article  PubMed  CAS  Google Scholar 

  • Vejsada, R., Tseng, J.L., Lindsay, R.M., Acheson, A., Aebischer, P., and Kato, A.C. (1998) Synergistic but transient rescue effects of BDNF and GDNF on axotomized neonatal motoneurons. Neuroscience 84, 129–139

    Article  PubMed  CAS  Google Scholar 

  • Wang, H.-G., Miyashita, T., Takayama, S., Sato, T., Torigoe, T., Krajewski, S., Tanaka, S., Hovey, L., III, Troppmair, J., Rapp, U.R., and Reed, J.C. (1994) Apoptosis regulation by interaction of Bcl-2 protein and Raf-1 kinase. Oncogene 9, 2751–2756

    PubMed  CAS  Google Scholar 

  • Wayne, D.B. and Heaton, M.B. (1988) Retrograde transport of NGF by early chick embryo spinal cord motoneurons. Dev.Biol. 127, 220–223

    Article  PubMed  CAS  Google Scholar 

  • Wayne, D.B. and Heaton, M.B. (1990a) The ontogeny of specific retrograde transport of nerve growth factor by motoneurons of the brainstem and spinal cord. Dev.Biol. 138, 484–498

    Article  PubMed  CAS  Google Scholar 

  • Wayne, D.B. and Heaton, M.B. (1990b) The response of cultured trigeminal and spinal cord motoneurons to nerve growth factor. Dev.Biol. 138, 473–483

    Article  PubMed  CAS  Google Scholar 

  • Wiese, S., Metzger, F., Holtmann, B., and Sendtner, M. (1999) The role of p75NTR in modulating neurotrophin survival effects in developing motoneurons. Eur.J.Neurosci. 11, 1668–1676

    Article  PubMed  CAS  Google Scholar 

  • Wiese, S., Pei, G., Karch, C., Troppmair, J., Holtmann, B., Rapp, U.R., and Sendtner, M. (2001) Specific function of B-Raf in mediating survival of embryonic motoneurons and sensory neurons. Nat.Neurosci. 4, 137–142

    Article  PubMed  CAS  Google Scholar 

  • Winter, C.G., Saotome, Y., Saotome, I., and Hirsh, D. (1996) CNTF overproduction hastens onset of symptoms in motor neuron degeneration (mnd) mice. J.Neurobiol. 31, 370–378

    Article  PubMed  CAS  Google Scholar 

  • Wixler, V., Smola, U., Schuler, M., and Rapp, U. (1996) Differential regulation of Raf isozymes by growth versus differentiation inducing factors in PC 12 pheochromocytoma cells. FEBS Letters 385, 131–137

    Article  PubMed  CAS  Google Scholar 

  • Yamashita, T., Tucker, K.L., and Barde, Y.A. (1999) Neurotrophin binding to the p75 receptor modulates Rho activity and axonal outgrowth. Neuron 24, 585–593

    Article  PubMed  CAS  Google Scholar 

  • Yan, Q., Elliott, J., and Snider, W.D. (1992) Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature 360, 753–755

    Article  PubMed  CAS  Google Scholar 

  • Yan, Q., Snider, W.D., Pinzone, J.J., and Johnson, E.M., Jr. (1988) Retrograde transport of nerve growth factor (NGF) in motoneurons of developing rats: assessment of potential neurotrophic effects. Neuron 1, 335–343

    Article  PubMed  CAS  Google Scholar 

  • York, R.D., Yao, H., Dillon, T., Ellig, C.L., Eckert, S.P., McCleskey, E.W., and Stork, P.J. (1998) Rap1 mediates sustained MAP kinase activation induced by nerve growth factor. Nature 392, 622–626

    Article  PubMed  CAS  Google Scholar 

  • Yoshida, K., Taga, T., Saito, M., Suematsu, S., Kumanogoh, A., Tanaka, T., Fujiwara, H., Hirata, M., Yamagami, T., Nakahata, T., Hirabayashi, T., Yoneda, Y., Tanaka, K., Wang, W.Z., Mori, C., Shiota, K., Yoshida, N., and Kishimoto, T. (1996) Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders. Proc.Natl.Acad.Sci.U.S.A. 93, 407–411

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Klin. Neurobiologie, University of Würzburg, Josef-Schneider-Str.11, 97080, Würzburg, Germany

    M. Sendtner

Authors
  1. M. Sendtner
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Pharmakologisches Institut, Universität Heidelberg, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany

    Stefan Offermanns

  2. Institut für Pharmakologie und Toxikologie der Universität, Versbacher Straße 9, 97078, Germany

    Lutz Hein

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Sendtner, M. (2004). Neurotrophic Factors. In: Offermanns, S., Hein, L. (eds) Transgenic Models in Pharmacology. Handbook of Experimental Pharmacology, vol 159. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18934-0_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-18934-0_10

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62362-2

  • Online ISBN: 978-3-642-18934-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation