Abstract
The prion protein is considered as one of the membrane targets of the neurotoxic beta-amyloid during development of Alzheimer’s disease. We chose and synthesized peptide fragments that corresponded to the 17–33, 23–33, 95–110, and 101–115 sequences of the prion protein and are responsible for the betaamyloid binding. The effect of immunization with the peptides on the development of symptoms of Alzheimer’s disease was investigated on animals with an experimentally induced form of the disease. Immunization with either free 17–33 peptide or with protein conjugates of the 23–33 and 101–115 peptides was shown to restore spatial memory of the animals. Immunization with the 17–33 peptide was also shown to decrease the level of brain beta-amyloid and to recover morphofunctional parameters of the brain.
Similar content being viewed by others
Abbreviations
- BE:
-
subjected to a bulbectomy
- SO:
-
sham operated
- CFA:
-
complete Freund’s adjuvant
- Fmoc:
-
9-fluorenylmethoxycarbonyl
- IFA:
-
incomplete Freund’s adjuvant
- KLH:
-
keyhole limpet hemocyanin
- OVA:
-
ovalbumin
- PBS:
-
phosphate buffered saline
References
Prusiner, S.B., Proc. Natl. Acad. Sci. U.S.A., 1998. vol. 95, pp. 13363–13383.
Esiri, M.M., Carter, J., and Ironside, J.W., Neuropathol. Appl. Neurobiol., 2000, vol. 26, pp. 273–284.
Ferrer, I., Blanco, R., Carmona, M., Puig, B., Ribera, R., Rey, M.J., and Ribalta, T., Acta Neuropathol., 2001, vol. 101, pp. 49–56.
Kovacs, G.G., Zerbi, P., Voigtlander, T., Strohschneider, M., Trabattoni, G., Hainfellner, J.A., and Budka, H., Neurosci. Lett., 2002, vol. 329, pp. 269–272.
Parkin, E.T., Watt, N.T., Hussain, I., Eckman, E.A., Eckman, C.B., Manson, J.C., Baybutt, H.N., Turner, A.J., and Hooper, N.M., Proc. Natl. Acad. Sci. U.S.A., 2007, vol. 104, pp. 11062–11067.
Dermaut, B., Croes, E.A., Rademakers, R., Broeck, M., Cruts, M., Hofman, A., van Duijn, C.M., and Van Broeckhoven, C., Ann. Neurol., 2003, vol. 53, pp. 409–412.
Riemenschneider, M., Klopp, N., Xiang, W., Wagenpfeil, S., Vollmert, C., Müller, U., Förstl, H., Illig, T., Kretzschmar, H., and Kurz, A., Neurology, 2004, vol. 63, pp. 364–366.
Laurén, J., Gimbel, D.A., Nygaard, H.B., Gilbert, J.W., and Strittmatter, S.M., Nature, 2009, vol. 457, pp. 1128–1132.
Chung, E., Ji, Y., Sun, Y., Kascsak, R.J., Kascsak, R.B., Mehta, P.D., Strittmatter, S.M., and Wisniewski, T., BMC Neurosci., 2010, vol. 11, p. 130.
Spinner, D.S., Kascsak, R.B., Lafauci, G., Meeker, H.C., Ye, X., Flory, M.J., Kim, J.I., Schuller-Levis, G.B., Levis, W.R., Wisniewski, T., Carp, R.I., and Kascsak, R.J., J. Leukocyte Biol., 2007, vol. 81, pp. 1374–1385.
Bobkova, N.V., Medvinskaya, N.I., Kamynina, A.V., Aleksandrova, I.Y., Nesterova, I.V., Samokhin, A.N., Koroev, D.O., Filatova, M.P., Nekrasov, P.V., Abramov, A.Y., Leonov, S.V., and Volpina, O.M., Neurobiol. Learn. Mem., 2014, vol. 107, pp. 50–64.
Kamynina, A.V., Holmström, K.M., Koroev, D.O., Volpina, O.M., and Abramov, A.Y., Int. J. Biochem. Cell. Biol., 2013, vol. 45, pp. 899–907.
Peretz, D., Williamson, R.A., Kaneko, K., Vergara, J., Leclerc, E., Schmitt-Ulms, G., Mehlhorn, I.R., Legname, G., Wormald, M.R., Rudd, P.M., Dwek, R.A., Burton, D.R., and Prusiner, S.B., Nature, 2001, vol. 412, pp. 739–743.
White, A.R., Enever, P., Tayebi, M., Mushens, R., Linehan, J., Brandner, S., Anstee, D., Collinge, J., and Hawke, S., Nature, 2003, vol. 422, pp. 80–83.
Oboznaya, M.B., Gilch, S., Titova, M.A., Koroev, D.O., Volkova, T.D., Volpina, O.M., and Schätzl, H.M., Cell. Mol. Neurobiol., 2007, vol. 27, pp. 271–284.
Chen, S., Yadav, S.P., and Surewicz, W.K., J. Biol. Chemistry, 2010, vol. 285, pp. 26377–26383.
Kang, M., Kim, S.Y., An, S.S., and Ju, Y.R., Exp. Mol. Med., 2013, vol. 45, p. e34.
Stahl, N., Baldwin, M.A., Teplow, D.B., Hood, L., Gibson, B.W., Burlingame, A.L., and Prusiner, S.B., Biochemistry, 1993, vol. 32, pp. 1991–2002.
Vol’pina, O.M., Titova, M.A., Zhmak, M.N., Koroev, D.O., Oboznaya, M.B., Volkova, T.D., and Ivanov, V.T., Russ. J. Bioorg. Chem., 2002, vol. 28, pp. 349–356.
Hozumi, S., Nakagawasai, O., Tan-No, K., Niijima, F., Yamadera, F., Murata, A., Arai, Y., Yasuhara, H., and Tadano, T., Behav. Brain Res., 2003, vol. 138, pp. 9–15.
Bobkova, N.V., Nesterova, I.V., Dana, R., Dana, E., Nesterov, V.I., Aleksandrova, Y., Medvinskaya, N.I., and Samokhin, A.N., Neurosci. Behav. Physiol., 2004, vol. 34, no. 7, pp. 671–676.
Aleksandrova, I.Yu., Kuvichkin, V.V., Kashparov, I.A., Medvinskaya, N.I., Nesterova, I.V., Lunin, S.M., Samokhin, A.N., and Bobkova, N.V., Biochemistry (Moscow), 2004, vol. 69, pp. 176–180.
Immunochemical Protocols, 2nd ed., Methods in Molecular Biology, Vol. 80, Pound, J., Ed., Humana Press, 1998.
Volpina, O.M., Medvinskaya, N.I., Kamynina, A.V., Zaporozhskaya, Y.V., Aleksandrova, I.J., Koroev, D.O., Samokhin, A.N., Volkova, T.D., Arseniev, A.S., and Bobkova, N.V, Russ. J. Bioorg. Chem., 2014, vol. 40, pp. 417–422.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © O.M. Volpina, T.D. Volkova, N.I. Medvinskaya, A.V. Kamynina, Ya.V. Zaporozhskaya, I.Yu. Aleksandrova, D.O. Koroev, A.N. Samokhin, I.V. Nesterova, V.I. Deygin, N.V. Bobkova, 2015, published in Bioorganicheskaya Khimiya, 2015, Vol. 41, No. 2, pp. 145–153.
Rights and permissions
About this article
Cite this article
Volpina, O.M., Volkova, T.D., Medvinskaya, N.I. et al. Protective activity of fragments of the prion protein after immunization of animals with experimentally induced Alzheimer’s disease. Russ J Bioorg Chem 41, 125–132 (2015). https://doi.org/10.1134/S1068162015020168
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1068162015020168