[Immunization witha synthetic fragment 155-164 of neurotrophin receptor p75 prevents memory loss and decreases beta-amyloid level in mice with experimentally induced Alzheimer's disease].

Bioorganicheskaia khimiia Pub Date : 2014-07-01
O M Vol'pina, N I Medvinskaia, A V Kamynina, Ia V Zaporozhskaia, I Iu Aleksandrova, D O Koroev, A N Samokhin, T D Volkova, A S Arsen'ev, N V Bobkova
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Abstract

Neurotoxic beta-amyloid peptide plays an important role in the pathology of Alzheimer's disease. In aggregated form it binds to several proteins on the surface of the brain cells leading to their death. p75 receptor in- volved in supporting of cell balance is one of the targets for toxic beta-amyloid. We proposed that induction of antibodies against potential binding sites of p75 with beta-amyloid can be a promising approach towards new drug development for Alzheimer's disease therapy. Four potentially immunoactive fragments of p75 were chosen and chemically synthesized. Investigation of immunoprotective effect of the peptide fragments carried out in mice with experimentally induced form of Alzheimer's disease helped to reveal two fragments effectively preserving murine memory from impairment. Results obtained by ELISA biochemical analysis showed that only immunization with fragment p75 155-164 led to significant decrease in beta-amyloid level in the brain of the experimental mice. Thus, immunization with both fragments of p75 receptor is believed to be an effective tool for the development of new drugs against Alzheimer's disease.

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[神经营养蛋白受体p75合成片段155-164免疫可预防实验性诱导阿尔茨海默病小鼠的记忆丧失并降低β -淀粉样蛋白水平]。
神经毒性β -淀粉样肽在阿尔茨海默病的病理中起重要作用。它以聚集的形式与脑细胞表面的几种蛋白质结合,导致脑细胞死亡。P75受体参与细胞平衡的支持,是毒性β -淀粉样蛋白的靶点之一。我们提出,诱导针对p75与β -淀粉样蛋白潜在结合位点的抗体可能是开发阿尔茨海默病治疗新药的一种有希望的方法。选择4个具有潜在免疫活性的p75片段进行化学合成。在实验诱导的阿尔茨海默病小鼠中进行的肽片段的免疫保护作用研究有助于揭示两个片段有效地保护小鼠记忆免受损害。ELISA生化分析结果显示,仅免疫片段p75 155-164可导致实验小鼠脑内β -淀粉样蛋白水平显著降低。因此,p75受体的两个片段的免疫被认为是开发抗阿尔茨海默病新药的有效工具。
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