Yue Shen, Li Yue, Wang Xiaohua, Bai Hui, Xia Jun, Jiang Li, Ji Yong, Fan Leming, He Zhigang, Chen Qi
Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, People's Republic of China.
Life Sci. 2008 Jun 20;82(25-26):1249-55. doi: 10.1016/j.lfs.2008.04.009. Epub 2008 Apr 24.
Beta-amyloid (Abeta) has been suggested as a potent neurotoxic agent. The Abeta-targeted immunotherapy aims to clear diffuse amyloid deposits and reverse memory deficits in Alzheimer's disease. We generated a human single chain variable domain antibody fragment (scFv) against Abeta40, termed E3, by screening a phage antibody library. E3 scFv could recognize Abeta in human cerebral cortex. It was able not only to prevent the aggregation of Abeta but also to disrupt the Abeta preexisting fibrils. Moreover, the Abeta toxicity to SK-N-SH cells was attenuated by addition of E3 scFv. Our results indicate that site-directed human scFv might be a potential therapeutic agent for Alzheimer's disease.
β-淀粉样蛋白（Aβ）被认为是一种强效神经毒性剂。针对Aβ的免疫疗法旨在清除弥漫性淀粉样沉积物并逆转阿尔茨海默病中的记忆缺陷。我们通过筛选噬菌体抗体库产生了一种针对Aβ40的人单链可变域抗体片段（scFv），称为E3。E3 scFv能够识别人类大脑皮层中的Aβ。它不仅能够防止Aβ聚集，还能破坏预先存在的Aβ纤维。此外，添加E3 scFv可减轻Aβ对SK-N-SH细胞的毒性。我们的结果表明，定点人scFv可能是治疗阿尔茨海默病的潜在治疗剂。
