A hybrid molecule that prohibits amyloid fibrils and alleviates neuronal toxicity induced by β-amyloid (1-42)
A hybrid molecule that prohibits amyloid fibrils and alleviates neuronal toxicity induced by β-amyloid (1-42)
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DOI：
10.1016/j.bbrc.2005.01.030
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发表时间：
2005-03-25
影响因子：
3.1
通讯作者：
Yu, J
中科院分区：
文献类型：
--
作者：
Lee, KH;Shin, BH;Yu, J
寡聚淀粉样蛋白（A）肽或原纤维形成的抑制已成为开发阿尔茨海默病新药的主要治疗靶点。我们专注于通过合成阿魏酸和苯乙烯基苯的混合分子来开发抑制剂，苯乙烯基苯被称为纤维粘合剂。最初，进行基于细胞的测定以评价有效化合物。一个选定的效应，1，减轻了分化的SH-SY 5 Y人神经母细胞瘤细胞中的Abeta诱导的神经元毒性。通过硫磺素T荧光强度测定和透射电子显微镜图像监测，该效应物还可以抑制Abeta原纤维的形成。使用表面等离子体共振技术测量了I对固定到表面芯片的非纤维状单体样Abeta的强结合亲和力。数据表明，效应物改变了多聚体Abeta的平衡，抑制了致病性寡聚体或原纤维的形成。(C)2005年爱思唯尔公司All rights reserved.
Inhibition of oligomeric amyloid (A) peptide or fibril formation has emerged as a major therapeutic target for developing new drugs for Alzheimer's disease. We focused on developing inhibitors by synthesizing hybrid molecules of ferulic acid and styryl benzene, which has been known as a fibril binder. Initially, cell-based assay was carried out to evaluate the effective compound. A selected effector, 1, alleviated the Abeta-induced neuronal toxicity in differentiated SH-SY5Y human neuroblastoma cells. The effector could also inhibit Abeta fibril formation, monitored by thioflavin T fluorescence intensity assay and transmitted electron microscopic images. A strong binding affinity of I to non-fibrous monomer-like Abeta, which was immobilized to a surface chip, was measured using a surface plasmon resonance technique. The data suggest that the effector shifts the equilibrium of multimeric Abeta, inhibiting the pathogenic oligomer or fibril formation. (C) 2005 Elsevier Inc. All rights reserved.