Conformation-dependent single-chain variable fragment antibodies specifically recognize beta-amyloid oligomers
Conformation-dependent single-chain variable fragment antibodies specifically recognize beta-amyloid oligomers
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DOI：
10.1016/j.febslet.2008.12.064
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发表时间：
2009-02-04
期刊：
影响因子：
3.5
通讯作者：
Liu, Rui-tian
中科院分区：
文献类型：
--
作者：
Wang, Xiao-ping;Zhang, Jun-hua;Liu, Rui-tian
越来越多的证据表明，β-淀粉样蛋白（A β）寡聚体，而不是单体或纤维是主要的毒性剂，特异性抑制突触可塑性和长时程增强（LTP）在阿尔茨海默病（AD）。发现A β寡聚体毒性的中和可逆转记忆缺陷。在这里，我们报告了四个单链可变片段（scFv）抗体分离的幼稚人的scFv库噬菌体展示，特异性识别A β寡聚体，但不单体和。这些构象依赖性scFv抗体抑制A β纤维化和细胞毒性，并结合A β寡聚体上展示的相同类型的表位。这种特异性靶向毒性A β寡聚体的scFv抗体可能具有AD的潜在治疗和诊断应用。(c)2009年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Increasing evidence indicates that beta-amyloid (A beta) oligomers rather than monomers or fibrils are the major toxic agents that specifically inhibit synaptic plasticity and long-term potentiation (LTP) in Alzheimer's disease (AD). Neutralization of A beta oligomeric toxicity was found to reverse memory deficits. Here, we report four single-chain variable fragment (scFv) antibodies isolated from the naive human scFv library by phage display that specifically recognized A beta oligomers but not monomers and.brils. These conformation-dependent scFv antibodies inhibit both A beta fibrillation and cytotoxicity and bind to the same type of eptitope displayed on the A beta oligomers. Such scFv antibodies specifically targeting toxic A beta oligomers may have potential therapeutic and diagnostic applications for AD. (c) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.