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

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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).

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Correspondence to O. M. Vol’pina.

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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

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