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.
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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
Mattson, M.P., Nature, 2004, vol. 430, pp. 631–639.
Hardy, J. and Selkoe, D.J., Science, 2002, vol. 297, pp. 353–356.
LaFerla, F.M., Tinkle, B.T., Bieberich, C.J., Haudenschild, C.C., and Jay, G., Nat. Genet., 1995, vol. 9, pp. 21–30.
Tabira, T., Chui, D.H., and Kuroda, S., Front. Biosci., 2002, vol. 7, pp. a44–a49.
Blennow, K., de Leon, M.J., and Zetterberg, H., Lancet, 2006, vol. 368, pp. 387–403.
Kihara, T. and Shimohama, S., Acta Neurobiol. Exp., 2004, vol. 64, pp. 99–105.
Nagele, R.G., D’Andrea, M.R., Anderson, W.J., and Wang, H.Y., Neuroscience, 2002, vol. 110, pp. 199–211.
D’Andrea, M.R., Nagele, R.G., Wang, H.Y., Peterson, P.A., and Lee, D.H., Histopathology, 2001, vol. 38, pp. 120–134.
D’Andrea, M.R., Lee, D.H.S., Wang, H.-Y., and Nagele, R.G., Drug Development Research, 2002, vol. 56, pp. 194–200.
D’Andrea, M.R. and Nagele, R.G., Curr. Pharm. Des., 2006, vol. 12, pp. 677–684.
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.
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.
Bobkova, N.V., Nesterova, I.V., and Nesterov, V.I., BEBM, 2001, vol. 131, pp. 507–511.
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.
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.
Ujiie, M., Dickstein, D.L., Carlow, D.A., and Jefferies, W.A., Microcirculation, 2003, vol. 10, pp. 463–470.
Engelhardt, B., Results Probl. Cell Differ., 2006, vol. 43, pp. 259–280.
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.
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.
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.
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.
Morris, R.G.M., J. Neurosci. Methods, 1984, vol. 11, pp. 47–60.
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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.
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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
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DOI: https://doi.org/10.1134/S1068162008010056