Molecular Cloning of Human Growth Inhibitory Factor CDNA and Its Down-Regulation in Alzheimer’s Disease

  • S. Tsuji
  • H. Kobayashi
  • Y. Uchida
  • Y. Ihara
  • T. Miyatake
Part of the Advances in Behavioral Biology book series (ABBI, volume 44)


Alzheimer’s disease (AD) is the most common dementing illness in man (Mann et al., 1988). AD is characterized by the presence of numerous senile plaques and neurofibrillary tangles throughout the cerebral cortex (Hirano and Zimmerman 1962; Kidd 1964; Schoenberg et al., 1987; Yamaguchi et al., 1988; Wisniewski et al., 1989). The major protein in senile plaques has been identified as a 39 ~ 42-amino-acid polypeptide referred to as the β/A4 protein (Masters et al., 1985; Selkoe et al., 1986). The major component of neurofibrillary tangles has also been identified as tau, a microtubule-associated phosphoprotein (Kondo et al., 1988; Wischik et al., 1988). The molecular mechanisms which lead to neuronal loss, and the accumulation of senile plaques followed by neurofibrillary tangles in AD, however, remain unexplained.


Neurofibrillary Tangle Growth Inhibitory Activity Growth Inhibitory Factor Neurotrophic Activity Immunohistochemical Observation 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Amsnn, E. and Brosius, J., 1985, Gene 40: 183–190.CrossRefGoogle Scholar
  2. Appel, S.H., 1981, Ann. Neurol. 10: 499–505.PubMedCrossRefGoogle Scholar
  3. Braak, H., and Braak, E., 1988, Neuropathol. Appl. Neurobiol. 14: 39–44.PubMedCrossRefGoogle Scholar
  4. Chen, E.Y. and Seeburg, P.H., 1985, DNA 4: 165–170.PubMedCrossRefGoogle Scholar
  5. Chirgwin, J.M., Przybyla, A.E., MacDonald, R.J., and Rutter, W.J., 1979, Biochemistry 18: 5294–5299.PubMedCrossRefGoogle Scholar
  6. Garvey, J.S., and Chang, C.C., 1981, Science 214: 805–807.PubMedCrossRefGoogle Scholar
  7. Foster, R., Jahroudi, N., Varshney, U., and Gedamu, L., 1988, J. Biol. Chem. 263: 11528–11535.PubMedGoogle Scholar
  8. Hamer, D.H., 1986, Ann. Rev. Biochem. 55: 913–951.PubMedCrossRefGoogle Scholar
  9. Heguy., A., West, A., Richards, R.I., and Karin, M., 1986, Mol. Cell. Biol. 6: 2149–2157.PubMedGoogle Scholar
  10. Hirano, A., and Zimmerman, H.H., 1962, Arch. Neurol. 7: 227–242.PubMedCrossRefGoogle Scholar
  11. Ihara, Y.,1988, Brain Res. 459: 138–144.Google Scholar
  12. Karin, M., and Richards, R.I., 1982, Nature 299: 797–802.PubMedCrossRefGoogle Scholar
  13. Karin, M., Eddy, R., Henry, W.M., Haley, L.L., Byers, M.C., and Shows, T.B., 1984, Proc. Natl. Acad. Sci. U.S.A. 81: 5494–5498.PubMedCrossRefGoogle Scholar
  14. Karin, M., 1985, Cell 41: 9–10.PubMedCrossRefGoogle Scholar
  15. Kidd, M., 1964, Brain, 87: 307–320.PubMedCrossRefGoogle Scholar
  16. Kobayashi, H., Sakimura, K., Kuwano, R., Sato, S., Ikuta, F., Takahashi, Y., Miyatake, T., and Tsuji, S., 1990, J. Mol. Neurosci. 2: 29–34.PubMedCrossRefGoogle Scholar
  17. Kobayashi, H., Takahashi, H., Oyanagi, K., Ikuta, F., Miyatake, T., and Tsuji, S., 1991, J. Mol. Neurosci. 3: 59–64.PubMedCrossRefGoogle Scholar
  18. Kobayashi, H., Uchida, Y., Ihara, Y., Nakajima, K., Kohsaka, S., Miyatake, T. and Tsuji, S., 1993, Mol. Brain Res. 19: 188–194.PubMedCrossRefGoogle Scholar
  19. Kondo, J., Honda, T., Mori, H., Hamada, Y., Miura, R., Ogawara, M., and Ihara, Y., 1988, Neuron 1: 827–834.PubMedCrossRefGoogle Scholar
  20. Lehrach, H., Diamond, D., Wozney, J.M., and Boedtkey, H., 1977, Biochemistry 16: 4743–4751.PubMedCrossRefGoogle Scholar
  21. Maniatis, T., Fritsh, E.F., and Sambrook, J., 1982, Molecular Cloning, Cold Spring Harbor, Laboratory, New York.Google Scholar
  22. Mann, D.M.A., Marycyniuk, B., Yates, P.O., Neary, D., and Snowden, J.S., 1988, Neuropathol. Appl. Neurobiol. 14: 177–195.PubMedCrossRefGoogle Scholar
  23. Masters, C.L., Simms, G., Weinmann, N.A., Multhaup, G., McDonald, B.L. and Beyreuther, K., 1985, Proc. NatL Acad. Sci. U.S.A. 82: 4245–4249.PubMedCrossRefGoogle Scholar
  24. Rosenfeld, M.G., Kreibach, G., Popov, D., Kato, K., and Sabatini, D., 1982, J. Cell. Biol. 24, 93: 135–143.CrossRefGoogle Scholar
  25. Saiki, R.K., Gelfand, D.H., Stoffel, S., Scharf, S.J., Higuchi, R., Horn, G.T., Mullins, K.B., and Erlich, H.A., 1988, Science 239: 487–491.PubMedCrossRefGoogle Scholar
  26. Sanger, F., Niclen, S., and Coulson, A.R., 1977, Proc. Natl. Acad. Sci. U.S.A. 74: 5463–5467.Google Scholar
  27. Schmidt, C.J., Jubier, M.F. and Hamer, D.H. (1985) J. Biol. Chem., 260, 7731–7737PubMedGoogle Scholar
  28. Schoenberg, B.S., Kokmen, E., and Okazaki, H., 1987, Ann. Neurol. 22: 724–729.PubMedCrossRefGoogle Scholar
  29. Selkoe, D.J., Abraham, C.R., Podlinsky, M.B., and Duffy, L.K., 1986, J. Neurochem. 46: 1820–1834.PubMedCrossRefGoogle Scholar
  30. Tsuji, S., Kobayashi, H., Uchida, Y., Ihara, Y.. and Miyatake, T., 1992, EMBO J. 11: 4843–4850.PubMedGoogle Scholar
  31. Uchida, Y., Ihara, Y., and Tomonaga, M., 1988, Biochem. Biophys. Res. Commun. 150: 1263–1267.PubMedCrossRefGoogle Scholar
  32. Uchida, Y., and Tomonaga, M., 1989, Brain Res. 481: 190–193.PubMedCrossRefGoogle Scholar
  33. Uchida, Y. Tokio, K., Titani, K., Ihara, Y., and Tomonaga, M., 1991, Neuron 7: 337–347.PubMedCrossRefGoogle Scholar
  34. Varshney, U., Jahroudi, N., Foster, R., and Gedamu, L., 1986, Mol. Cell. Biol. 6: 26–37.PubMedGoogle Scholar
  35. Wahl, G.M., Stern, M., and Stark, G.R., 1979, Proc. Natl. Acad. Sci. U.S.A. 76: 3683–3687PubMedCrossRefGoogle Scholar
  36. Walter, P., Gilmore, R., and Blobel, G., 1984, Cell, 38: 5–8.PubMedCrossRefGoogle Scholar
  37. Watson, M.E.E., 1984, Nucleic Acids Res. 12: 5145–5164.PubMedCrossRefGoogle Scholar
  38. West, A.K., Stallings, R., Hildebrand, C.E., Chin, R., Karin, M., and Richards, R.I., 1990, Genomics 8: 513–518.PubMedCrossRefGoogle Scholar
  39. Wischik, C., Novak, M., Thagersen, H.C., Edwards, P.C., Runswick, M.J., Jakes, R., Walka, J.E., Milstein, C., Rath, M., and Klug, A., 1988, Proc. Natl. Acad. Sci. U.S.A., 85: 4506–4510.CrossRefGoogle Scholar
  40. Wisniewski, H.H., Baucher, C., Barcikowski, M., Wen, G.Y., and Currie, J., 1989, Acta Neuropathol. 78: 337–347.CrossRefGoogle Scholar
  41. Yamaguchi, H., Hirai, S., Morimatsu, S., Shoji M., and Lhara, Y., 1988, Acta Neuropathol. (Berl) 76: 54 1549.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • S. Tsuji
    • 1
  • H. Kobayashi
    • 1
  • Y. Uchida
    • 2
  • Y. Ihara
    • 3
  • T. Miyatake
    • 4
  1. 1.Department of NeurologyBrain Research Institute Niigata UniversityAsahimachi-dori, Niigata 951Japan
  2. 2.Departments of NeuropathologyTokyo Metropolitan Institute of GerontologyItabashiku, Tokyo 173Japan
  3. 3.Department of Neuropathology Institute of Brain Research, Faculty of MedicineUniversity of TokyoBunkyoku, Tokyo 113Japan
  4. 4.Department of NeurologyTokyo Medical and Dental UniversityYushima, Bunkyoku, Tokyo 113Japan

Personalised recommendations