Skip to main content

Advertisement

SpringerLink
Log in

Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

Alzheimer's disease1 is characterized by cerebral deposits of amyloid β-protein (AP) as senile plaque core and vascular amyloid2–6, and a complementary DNA encoding a precursor of this protein (APP) has been cloned from human brain7–11. From a cDNA library of a human glioblastoma cell line, we have isolated a cDNA identical to that previously reported, together with a new cDNA which contains a 225-nucleotide insert. The sequence of the 56 a mi no acids at the N-terminal of the protein deduced from this insert is highly homologous to the basic trypsin inhibitor family12, and the lysate from COS-1 cells transfected with the longer APP cDNA showed an increased inhibition of trypsin activity. Partial sequencing of the genomic DNA encoding APP showed that the 225 nucleotides are located in two exons. At least three messenger RNA species, apparently transcribed from a single APP gene by alternative splicing, were found in human brain. We suggest that protease inhibition by the longer APP(s) could be related to aberrant APP catabolism.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Alzheimer, A. Allg. Z. Psychiat. 64, 146–148 (1907).

    Google Scholar 

  2. Mountjov, C. Q. et al. J. Neurol Sci. 57, 89–103 (1982).

    Article  Google Scholar 

  3. Glenner, G. G. & Wong, C. W. Biochem. biophys. Res. Commun. 120, 885–890 (1984).

    Article  CAS  Google Scholar 

  4. Masters, C. L. et al. Proc. natn. Acad. Sci. U.S.A. 82, 4245–4249 (1985).

    Article  ADS  CAS  Google Scholar 

  5. Wong, C. W. et al. Proc. natn. Acad. Sci. U.S.A. 82, 8729–8732 (1985).

    Article  ADS  CAS  Google Scholar 

  6. Masters, C. L. et al. EMBO J. 4, 2757–2763 (1985).

    Article  CAS  Google Scholar 

  7. Kang, J. et al. Nature 325, 733–736 (1987).

    Article  ADS  CAS  Google Scholar 

  8. Robakis, N. K. et al. Proc. natn. Acad. Sci. U.S.A. 84, 4190–4194 (1987).

    Article  ADS  CAS  Google Scholar 

  9. Goldgaber, D., Lerman, M. I., McBride, O. W., Saffiotti, U. & Gajdusek, D. C. Science 235, 877–880 (1987).

    Article  ADS  CAS  Google Scholar 

  10. Tanzi, R. E. et al. Science 235, 880–884 (1987).

    Article  ADS  CAS  Google Scholar 

  11. Goedert, M. EMBO J. 6, 3627–3632 (1987).

    Article  CAS  Google Scholar 

  12. Laskowski, M. Jr & Kato, I. A. Rev. Biochem. 49, 593–626 (1980).

    Article  CAS  Google Scholar 

  13. Wunderer, G. et al. Meth. Enzym. 80, 816–820 (1981).

    Article  CAS  Google Scholar 

  14. Strydom, D. J. & Joubert, F. J. Hoppe-Seyler's Z. Physiol. Chem. 362, S. 1377–1384 (1981).

    Article  CAS  Google Scholar 

  15. Breathnach, R. & Chambon, P. A. Rev. Biochem. 50, 349–383 (1981).

    Article  CAS  Google Scholar 

  16. St. George-Hyslop, P. H. et al. Science 238, 664–666 (1987).

    Article  ADS  CAS  Google Scholar 

  17. Tanzi, R. E., Bird, E. D., Latt, S. A. & Neve, R. L. Science 238, 666–669 (1987).

    Article  ADS  CAS  Google Scholar 

  18. Podlisny, M. B., Lee, G. & Selkoe, D. J. Science 238, 669–671 (1987).

    Article  ADS  CAS  Google Scholar 

  19. Van Broeckhoven, C. et al. Nature 329, 153–155 (1987).

    Article  ADS  CAS  Google Scholar 

  20. Tanzi, R. E. et al. Nature 329, 156–157 (1987).

    Article  ADS  CAS  Google Scholar 

  21. Kassel, B. Meth. Enzym. 19, 844–852 (1970).

    Article  Google Scholar 

  22. Kanaoka, Y. et al. Chem. pharm. Bull. 25, 3126–3128 (1977).

    Article  CAS  Google Scholar 

  23. Chirgwin, J. M., Przybyla, A. E., MacDonald, R. J. & Rutter, W. J. Biochemistry 18, 5294–5299 (1979).

    Article  CAS  Google Scholar 

  24. Sanger, F. Science 214, 1205–1210 (1981).

    Article  ADS  CAS  Google Scholar 

  25. Henikoff, S. Gene 28, 351–359 (1984).

    Article  CAS  Google Scholar 

  26. Thomas, P. S. Proc. natn. Acad. Sci. U.S.A. 77, 5201–5205 (1980).

    Article  ADS  CAS  Google Scholar 

  27. Chan, V. -L. & Smith, M. Nucleic Acids Res. 12, 2407–2419 (1984).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Bio-Science Laboratory, Life Science Research Laboratories, Asahi Chemical Industry Co. Ltd., 2-1 Samejima, Fuji-Shi, Shizuoka, 416, Japan

    Nobuya Kitaguchi, Yasuyuki Takahashi, Yasuo Tokushima, Satoshi Shiojiri & Hirataka Ito

Authors
  1. Nobuya Kitaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasuyuki Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yasuo Tokushima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Satoshi Shiojiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hirataka Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kitaguchi, N., Takahashi, Y., Tokushima, Y. et al. Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature 331, 530–532 (1988). https://doi.org/10.1038/331530a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/331530a0

  • Springer Nature Limited

This article is cited by

Search

Navigation