【作者】 丁姝姝； 施国跃； 朱安伟；

【Author】 Shushu Ding;Guoyue Shi;Anwei Zhu;School of Chemistry and Molecular Engineering,East China Normal University;School of Pharmacy,Nantong University;

【机构】 华东师范大学化学与分子工程学院； 南通大学药学院；

【摘要】 β-淀粉样蛋白（Aβ）的神经毒性在阿尔茨海默症（AD）的病情发展过程中发挥着重要作用。除形成斑块沉积外,Aβ可与细胞膜结合形成门控离子通道并调节离子传输,加速AD病情发展^[1,2]。基于此,开发具有高可控性和离子传输效率的仿生离子通道,不仅利于解析Aβ门控通道离子迁移过程,还可促进疾病的早期诊断及治疗。本文基于仿生设计理念,制备以唾液酸为识别单元,柔性聚（N-异丙基丙烯酰胺）（PNIPAAm）为骨架的刺激响应聚合物;以玻璃锥形纳米孔为主体,进一步构筑Aβ调节智能纳米通道系统,通过Aβ识别诱导聚合物构象变化实现门控功能;利用玻璃锥形纳米孔的限域效应,聚合物多重氢键协同作用可实现Aβ单体的超灵敏检测,检测限可达飞摩尔级,此外该方法可实现AD小鼠不同脑区Aβ单体的直接测定;在此基础上,准确获取药物干预下Aβ门控通道离子传输变化规律,为疾病的早期诊断、药物研发提供科学有效的支撑。更多还原

【Abstract】 The neurotoxicity of amyloid-β(Aβ) plays an important role in the pathogenesis of Alzheimer’s disease(AD).The insertion of Aβ into the membrane may result in the formation of Aβ ion channels,inducing cell death by apoptosis.The development of biomimetic ion channels with excellent controllability and high ion transmission efficiency is of great significance for early diagnosis of disease.Inspired by biomimetic concept,a novel stimuli-responsive copolymer containing sialic acid as the recognition center and the functional switching units of poly(N-isopropylacrylamide) were synthesized and further developed into intelligent nanochannel system.The recognition of Aβ can fulfill gating function through the conformation change of copolymer.The smart hydrogen bonding network within the confined space significantly improved the detection sensitivity of Aβ monomer.Besides,this system with remarkable analytical performance was successfully applied to evaluate the concentration of Aβ monomer in live mouse brain with AD.On this basis,we explored the changes of ion transmission in the Aβ-gated channel upon the stimulation of drugs,which is beneficial for progressing our understanding of the role that Aβ plays in physiological and pathological events in the disease.更多还原