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首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >Novel amyloid-beta specific scFv and VH antibody fragments from human and mouse phage display antibody libraries.
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Novel amyloid-beta specific scFv and VH antibody fragments from human and mouse phage display antibody libraries.

机译：来自人和小鼠噬菌体的新型淀粉样蛋白β特异性scFv和VH抗体片段展示抗体库。

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Anti-amyloid immunotherapy has been proposed as an appropriate therapeutic approach for Alzheimer's disease (AD). Significant efforts have been made towards the generation and assessment of antibody-based reagents capable of preventing and clearing amyloid aggregates as well as preventing their synaptotoxic effects. In this study, we selected a novel set of human anti-amyloid-beta peptide 1-42 (Abeta1-42) recombinant monoclonal antibodies in a single chain fragment variable (scFv) and a single-domain (VH) format. We demonstrated that these antibody fragments recognize in a specific manner amyloid-beta deposits in APP/Tg mouse brains, inhibit toxicity of oligomeric Abeta1-42 in neuroblastoma cell cultures in a concentration-dependent manner and reduced amyloid deposits in APP/Tg2576 mice after intracranial administration. These antibody fragments recognize epitopes in the middle/C-terminus region of Abeta, which makes them strong therapeutic candidates due to the fact that most of the Abeta species found in the brains of AD patients display extensive N-terminus truncations/modifications.
机译：已经提出抗淀粉样蛋白免疫疗法作为阿尔茨海默氏病（AD）的适当治疗方法。在产生和评估能够预防和清除淀粉样蛋白聚集物以及防止其突触毒性作用的基于抗体的试剂方面已经做出了巨大的努力。在这项研究中，我们以单链片段变量（scFv）和单域（VH）格式选择了一组新型的人类抗淀粉样蛋白肽1-42（Abeta1-42）重组单克隆抗体。我们证明了这些抗体片段以特定的方式识别APP / Tg小鼠大脑中的淀粉样β沉积物，以浓度依赖的方式抑制神经母细胞瘤细胞培养物中寡聚Abeta1-42的毒性，并减少了颅内颅内APP / Tg2576小鼠中的淀粉样蛋白沉积行政。这些抗体片段可识别Abeta中部/ C端区域的表位，由于在AD患者大脑中发现的大多数Abeta物种都具有广泛的N端截短/修饰，因此使其成为强大的治疗候选物。

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