Ciliary Neurotrophic Factor (CNTF): Possible Implications in the Pathogenesis of Amyotrophic Lateral Sclerosis

  • Richard W. Orrell
  • Russell J. M. Lane
  • Jackie S. de Belleroche
Part of the GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia book series (GWUN)


Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, primarily affecting both upper and lower motor neurons. The median age of onset is around 68 years, and median survival approximately 2 years, although with significant variability1. The pathogenesis is unknown, but the recognition of mutations in the gene for copper/zinc Superoxide dismutase (SOD-1)2 in a proportion of patients (around 1–2% of all cases), almost all of whom have a family history of the condition, has provided fruitful avenues of research3. Nevertheless, the mechanism by which these mutations lead to the expression of the disease is not yet established4,5.


Amyotrophic Lateral Sclerosis Motor Neuron Nerve Growth Factor Motor Neuron Disease Lower Motor Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    S. Yoshida, D.W. Mulder, L.T. Kurland, C. Chu, and H. Okazaki, Follow-up study on amyotrophic lateral sclerosis in Rochester, Minn., 1925 through 1984, Neuroepidemiology 5:61–70 (1986).PubMedCrossRefGoogle Scholar
  2. 2.
    D.R. Rosen, T. Siddique, D Patterson, DA. Figlewicz, P. Sapp, A. Hentati, D. Donaldson, J. Goto, J.P. O’Regan, H.-X. Deng, Z. Rahmani, A. Kirzus, D. McKenna-Yasek, A. Cayabyab, S.M. Gaston, R. Berger, R.E. Tanzi, JJ. Haperin, B. Herzfeldt, R. Van den Bergh, W.-Y. Hung, T. Bird, G. Deng, D.W. Mulder, C. Smyth, N.G. Laing, E. Soriano, M.A. Pericack-Vance, J. Haines, G.A. Rouleau, J.S. Gusella, H.R. Horvitz, and R.H. Brown, Mutations in Cu/Zn Superoxide dismutase are associated with familial amyotrophic lateral sclerosis, Nature 362:59–62 (1993).PubMedCrossRefGoogle Scholar
  3. 3.
    R.W. Orrell and J. de Belleroche, Superoxide dismutase and ALS, Lancet 344:1651–1652 (1994).PubMedCrossRefGoogle Scholar
  4. 4.
    R.H. Brown. Amyotrophic lateral sclerosis: recent insights from genetics and transgenic mice. Gell 80:687–692 (1995).Google Scholar
  5. 5.
    R. Orrell, J. de Belleroche, S. Marklund, F. Bowe, and R. Hallewell, A novel SOD mutant and ALS, Nature 374:504–505 (1995).PubMedCrossRefGoogle Scholar
  6. 6.
    L.P. Rowland, Amyotrophic lateral sclerosis: human challenge for neuroscience, Proc Natl Acad Sci USA 92:1251–1253 (1995).PubMedCrossRefGoogle Scholar
  7. 7.
    J. de Belleroche, R. Orrell, and A. King, Familial amyotrophic lateral sclerosis/motor neurone disease (FALS): a review of current developments, J Med Genet (in press).Google Scholar
  8. 8.
    J. Drago, T.J. Kilpatrick, S.A. Kolbar, and P.S. Talman, Growth factors: potential therapeutic applications in neurology, J Neural Neurosurg Psychiatry 57:1445–1450 (1994).CrossRefGoogle Scholar
  9. 9.
    Q. Yan, C, Matheson, and O.T. Lopez, In vivo neurotrophic effects of GDNF on neonatal and adult facial motor neurons. Nature 373:341–344 (1995).PubMedCrossRefGoogle Scholar
  10. 10.
    R.W. Orrell, R.J.M. Lane, and R.J. Guiloff, Recent developments in the drug treatment of motor neurone disease, Br Med J 309:140–141 (1994).CrossRefGoogle Scholar
  11. 12.
    Y. Arakawa, M. Sendtner, and H. Thoenen, Survival effect of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines, J Neuroscience 10:3507–3515 (1990).Google Scholar
  12. 12.
    G. Barbin, M. Manthorpe, and S. Varon. Purification of the chick eye ciliary neurotrophic factor, J Neurochem 43:1468–1478 (1984).PubMedCrossRefGoogle Scholar
  13. 13.
    M. Sendtner, G. W. Kreutzberg, and H. Thoenen. Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature 345:440–441 (1990).PubMedCrossRefGoogle Scholar
  14. 14.
    M. Sendtner, H. Schmalbruch, K.A. Stockli, P. Carroll, G.W. Kreutzberg, and H. Thoenen, Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy, Nature 358:502–504.Google Scholar
  15. 15.
    Y.W. Kwon, and M.E. Gurney, Systemic injections of ciliary neurotrophic factor induce sprouting by adult motor neurons, NeuroReport 5:789–792 (1994).PubMedCrossRefGoogle Scholar
  16. 16.
    Y. Masu, E. Wolf, B. Holtmann, M. Sendtner, G. Brem, and H. Thoenen, Disruption of the CNTF gene results in motor neuron degeneration, Nature 365:27–32 (1993).PubMedCrossRefGoogle Scholar
  17. 17.
    A. Lam, F. Fuller, J. Miller, J. Kloss, M. Manthorpe, S. Varon, and B. Cordell, Sequence and structural organization of the human gene encoding ciliary neurotrophic factor, Gene 102:271–276 (1991).PubMedCrossRefGoogle Scholar
  18. 18.
    A. Negro, E. Tolosano, S.D. Skaper, I. Martinin, L. Callegaro, L. Silengo, F. Fiorini, and F. Altruda, Cloning and expression of human ciliary neurotrophic factor, Eur J Biochem 201:289–294 (1991).PubMedCrossRefGoogle Scholar
  19. 19.
    R. Takahashi, H. Yokoji, H. Misawa, M. Hayashi, J. Hu, and T. Deguchi, A null mutation in the human CNTF gene is not causally related to neurological diseases. Nature Genetics 7:79–84 (1994).PubMedCrossRefGoogle Scholar
  20. 20.
    R. Takahashi, H. Yokoji, H. Misawa, M. Hayashi, J. Hu, and T. Deguchi, A null mutation in the human CNTF gene is not causally related to neurological diseases, Nature Genetics 7:215 (1994).Google Scholar
  21. 21.
    R.W. Orrell, A. W. King, R.J.M. Lane, and J.S. de Belleroche, Investigation of a null mutation of the CNTF gene in familial amyotrophic lateral sclerosis, J Neurol Sci (in press).Google Scholar
  22. 22.
    P. Anand, A. Parrett, J. Martin, S. Zeman, P. Foley, M. Swash, P.N. Leigh, J.M. Cedarbaum, R.M. Lindsay, R.E. Williams-Chestnut, and D.V. Sinicropi, Regional changes of ciliary neurotrophic factor and nerve growth factor levels in post mortem spinal cord and cerebral cortex from patients with motor neuron disease, Nature Medicine 1:168–172 (1995).PubMedCrossRefGoogle Scholar
  23. 23.
    F. Dittrich, H. Thoenen, and M. Sendtner, Ciliary neurotrophic factor: pharmacokinetics and acute-phase response in rat, Ann Neurol 35:151–163 (1994).PubMedCrossRefGoogle Scholar
  24. 24.
    H. Mitsumoto, K. Ikeda, B. Klinkosz, J.M. Cedarbaum, V. Wong, and R.M. Lindsay, Arrest of motor neuron disease in wobbler mice cotreated with CNTF and BDNF, Science 265:1107–1110 (1994).PubMedCrossRefGoogle Scholar
  25. 25.
    G. Bensimon, L. Lacomblez, V. Meininger, and the ALS/Riluzole Study Group, A controlled trial of riluzole in amyotrophic lateral sclerosis, N Engt J Med 330:613–22 (1994).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Richard W. Orrell
    • 1
    • 2
  • Russell J. M. Lane
    • 2
  • Jackie S. de Belleroche
    • 1
  1. 1.Department of BiochemistryCharing Cross and Westminster Medical SchoolLondonEngland
  2. 2.Academic Unit of NeuroscienceCharing Cross and Westminster Medical SchoolLondonEngland

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