Antiamyloidogenic Activity of Aβ42-Binding Peptoid in Modulating Amyloid Oligomerization.
Antiamyloidogenic Activity of Aβ42-Binding Peptoid in Modulating Amyloid Oligomerization.
复制标题
DOI：
10.1002/smll.201602857
复制
发表时间：
2017
期刊：
影响因子：
13.3
通讯作者：
Zijian Zhao;Ling Zhu;Haiyun Li;Peng Cheng;Jiaxi Peng;Yudan Yin;Yang Yang-Yang;Chen Wang;Zhiyuan Hu
中科院分区：
文献类型：
--
作者：
Zijian Zhao;Ling Zhu;Haiyun Li;Peng Cheng;Jiaxi Peng;Yudan Yin;Yang Yang-Yang;Chen Wang;Zhiyuan Hu
淀粉样蛋白β（amyloid β，Aβ）的寡聚化和聚集在阿尔茨海默病（Alzheimer 'sdisease，AD）的发病机制中起着重要作用。调节Aβ寡聚体和原纤维形成的分子结合剂在AD治疗中具有广阔的应用前景。通过使用表面等离子体共振成像筛选类肽文库，鉴定了对Aβ42具有高亲和力的淀粉样蛋白抑制类肽1（AIP 1）。AIP 1可抑制Aβ42寡聚化和纤颤，并通过降低与细胞膜通透性相关的Aβ42寡聚体含量来挽救Aβ 42诱导的细胞毒性。分子对接表明AIP 1的结合位点可能位于Aβ42的N端。还揭示了使用体外血脑屏障（BBB）模型的AIP 1的血脑屏障（BBB）渗透性。这项工作提供了一个战略的设计和开发基于肽类抗淀粉样蛋白的药物。所获得的淀粉样蛋白抑制肽在AD的治疗应用中显示出前景。
The oligomerization and aggregation of amyloid β (Aβ) play central role in the pathogenesis of Alzheimer's disease (AD). Molecular binding agents for modulating the formation of Aβ oligomers and fibrils have promising application potential in AD therapies. By screening a peptoid library using surface plasmon resonance imaging, amyloid inhibitory peptoid 1 (AIP1) that has high affinity to Aβ42 is identified. AIP1 is demonstrated to inhibit Aβ42 oligomerization and fibrillation and to rescue Aβ42-induced cytotoxicity through decreasing the content of Aβ42 oligomers that is related to cell membrane permeability. Molecular docking suggests that the binding sites of AIP1 may be at the N-terminus of Aβ42. The blood-brain barrier (BBB) permeability of AIP1 using an in vitro BBB model is also revealed. This work provides a strategy for the design and development of peptoid-based antiamyloidogenic agents. The obtained amyloid inhibitory peptoid shows prospects in the therapeutic application in AD.