Skip to main content

New approaches to the immunotherapy of Alzheimer’s disease with the synthetic fragments of α7 subunit of the acetylcholine receptor

Abstract

The effect of immunization with the synthetic fragments of the α7 subunit of the acetylcholine nicotine receptor on the spatial memory of mice subjected to olfactory bulbectomy, which causes the development of the neurodegenerative disease of Alzheimer’s type, was studied. NMRI mice were immunized with the KLH conjugates of two peptide fragments of the N-terminal fragment of the α7 subunit extracellular fragment, subjected to olfactory bulbectomy to cause the development of the neurodegenerative disease of Alzheimer’s type, and then the state of the spatial memory was evaluated. It was shown that 20% of bulbectomized mice immunized with N-terminal 1–23 fragment exhibited good spatial memory after training. Immunization with the peptide construct (159–167)-(179–188) consisting of two hydrophilic exposed regions of α7-subunit induced good spatial memory in 50% of bulbectomized mice, while in the control group, which received only KLH, none of animals were learned. Thus, the development of immunotherapy with peptide (159–167)-(179–188) seems to be a promising approach to prophylaxis and treatment of Alzheimer’s disease.

This is a preview of subscription content, access via your institution.

Abbreviations

ACR:

acetylcholine receptor

AD:

Alzheimer’s disease

BE animals:

animals (mice) subjected to olfactory bulbectomy

CFA:

complete Freund’s adjuvant

Fmoc:

9-fluorenylmethoxycarbonyl

IFA:

incomplete Freund’s adjuvant

KLH:

keyhole limpet hemocyanin

PBS:

phosphate buffered saline, 0.15 M NaCl in 0.01 M NaH2PO4 (pH 7.4).

References

  1. Mattson, M.P., Nature, 2004, vol. 430, pp. 631–639.

    CAS  Article  PubMed  Google Scholar 

  2. Hardy, J. and Selkoe, D.J., Science, 2002, vol. 297, pp. 353–356.

    CAS  Article  PubMed  Google Scholar 

  3. LaFerla, F.M., Tinkle, B.T., Bieberich, C.J., Haudenschild, C.C., and Jay, G., Nat. Genet., 1995, vol. 9, pp. 21–30.

    CAS  Article  PubMed  Google Scholar 

  4. Tabira, T., Chui, D.H., and Kuroda, S., Front. Biosci., 2002, vol. 7, pp. a44–a49.

    CAS  Article  PubMed  Google Scholar 

  5. Blennow, K., de Leon, M.J., and Zetterberg, H., Lancet, 2006, vol. 368, pp. 387–403.

    CAS  Article  PubMed  Google Scholar 

  6. Kihara, T. and Shimohama, S., Acta Neurobiol. Exp., 2004, vol. 64, pp. 99–105.

    Google Scholar 

  7. Nagele, R.G., D’Andrea, M.R., Anderson, W.J., and Wang, H.Y., Neuroscience, 2002, vol. 110, pp. 199–211.

    CAS  Article  PubMed  Google Scholar 

  8. D’Andrea, M.R., Nagele, R.G., Wang, H.Y., Peterson, P.A., and Lee, D.H., Histopathology, 2001, vol. 38, pp. 120–134.

    Article  PubMed  Google Scholar 

  9. D’Andrea, M.R., Lee, D.H.S., Wang, H.-Y., and Nagele, R.G., Drug Development Research, 2002, vol. 56, pp. 194–200.

    Article  Google Scholar 

  10. D’Andrea, M.R. and Nagele, R.G., Curr. Pharm. Des., 2006, vol. 12, pp. 677–684.

    Article  PubMed  Google Scholar 

  11. Aleksandrova, I.Yu., Kuvichkin, V.V., Kashparov, I.V., Medvinskaya, N.I., Nesterova, I.V., Lunin, S.M., Samokhin, A.N., and Bobkova, N.V., Biokhimiya (Moscow), 2004, vol. 69, pp. 218–224.

    Google Scholar 

  12. Bobkova, N.V., Nesterova, I.V., Medvinskaya, N.I., Aleksandrova, I.Y., Samokhin, A.N., Gershovich, J.G., Gershovich, P.M., and Yashin, V.A., in New Trends in Alzheimer and Parkinson Related Disorders: ADPD 2005, Fisher, A., Hanin, I., Memo, M., and Stocchi, F., Eds., Medimond, 2005, pp. 91–95.

  13. Bobkova, N.V., Nesterova, I.V., and Nesterov, V.I., BEBM, 2001, vol. 131, pp. 507–511.

    Google Scholar 

  14. Volpina, O.M., Titova, M.A., Koroev, D.O., Volkova, T.D., Oboznaya, M.V., Zhmak, M.N., Alekseev, T.A., and Tsetlin, V.I., Bioorg. Khim., 2006, vol. 32, pp. 169–175; Rus. J. Bioorg. Chem., 2006, vol. 32, pp. 154–159.

    CAS  Google Scholar 

  15. Koroev, D.O., Titova, M.A., Volkova, T.D., Oboznaya, M.V., Filatova, M.R., Fufatshova, E.N., Zhmak, M.N., Tsetlin, V.I., Bobkova, N.V., and Volpina, O.M., Bioorg. Khim., 2007, vol. 33, pp. 442–447; Rus. J. Bioorg. Chem., 2007, vol. 33, pp. 410–414.

    CAS  PubMed  Google Scholar 

  16. Ujiie, M., Dickstein, D.L., Carlow, D.A., and Jefferies, W.A., Microcirculation, 2003, vol. 10, pp. 463–470.

    CAS  PubMed  Google Scholar 

  17. Engelhardt, B., Results Probl. Cell Differ., 2006, vol. 43, pp. 259–280.

    CAS  Article  PubMed  Google Scholar 

  18. Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., Kholodenko, D., Lee, M., Liao, Z., Lieberburg, I., Motter, R., Mutter, L., Soriano, F., Shopp, G., Vasquez, N., Vandevert, C., Walker, S., Wogulis, M., Yednock, T., Games, D., and Seubert, P., Nature, 1999, vol. 400, pp. 173–177.

    CAS  Article  PubMed  Google Scholar 

  19. Maier, M., Seabrook, T.J., Lazo, N.D., Jiang, L., Das, P., Janus, C., and Lemere, C.A., J. Neurosci., 2006, vol. 26, pp. 4717–4728.

    CAS  Article  PubMed  Google Scholar 

  20. Orgogozo, J.M., Gilman, S., Dartigues, J.F., Laurent, B., Puel, M., Kirby, L.C., Jouanny, P., Dubois, B., Eisner, L., Flitman, S., Michel, B.F., Boada, M., Frank, A., and Hock, C., Neurology, 2003, vol. 61, pp. 46–54.

    CAS  PubMed  Google Scholar 

  21. Koroev, D.O., Kotel’nikova, O.V., Zhmak, M.N., Kupriyanova, M.A., Agafonova, S.A., Alliluev, A.R., Litvinov, I.S., Nesmejanov, V.A., and Ivanov, V.T., Bioorg. Khim., 2000, vol. 26, pp. 323–329; Rus. J. Bioorg. Chem., 2000, vol. 26, pp. 291–296.

    CAS  PubMed  Google Scholar 

  22. Morris, R.G.M., J. Neurosci. Methods, 1984, vol. 11, pp. 47–60.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to O. M. Vol’pina.

Additional information

Original Russian Text © O.M. Vol’pina, T.D. Volkova, M.A. Titova, Yu.G. Gershovich, N.I. Medvinskaya, A.N. Samokhin, A.V. Kamynina, V.S. Shalgunov, D.O. Koroev, M.P. Filatova, M.B. Obosnaya, and N.V. Bobkova, 2008, published in Bioorganicheskaya Khimiya, 2008, Vol. 34, No. 1, pp. 50–55.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Vol’pina, O.M., Volkova, T.D., Titova, M.A. et al. New approaches to the immunotherapy of Alzheimer’s disease with the synthetic fragments of α7 subunit of the acetylcholine receptor. Russ J Bioorg Chem 34, 43–48 (2008). https://doi.org/10.1134/S1068162008010056

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162008010056

Key words

  • acetylcholine receptor
  • α7 subunit
  • Alzheimer’s disease
  • olfactory bulbectomy
  • spatial memory
  • synthetic peptides