化学
细胞毒性
神经保护
淀粉样蛋白(真菌学)
多金属氧酸盐
蛋白质聚集
β淀粉样蛋白
活力测定
氢键
铂金
生物物理学
阿尔茨海默病
药理学
细胞
生物化学
疾病
医学
生物
分子
体外
内科学
有机化学
无机化学
催化作用
作者
Jing Zhao,Kexin Li,Kaiwei Wan,Tiedong Sun,Nannan Zheng,Fanjiao Zhu,Jichao Ma,Jia Jiao,Tianchan Li,Jinyuan Ni,Xinghua Shi,Hui Wang,Qiang Peng,Jing Ai,Wanhai Xu,Shaoqin Liu
标识
DOI:10.1002/anie.201910521
摘要
Aggregated β-amyloid (Aβ) is widely considered as a key factor in triggering progressive loss of neuronal function in Alzheimer's disease (AD), so targeting and inhibiting Aβ aggregation has been broadly recognized as an efficient therapeutic strategy for curing AD. Herein, we designed and prepared an organic platinum-substituted polyoxometalate, (Me4 N)3 [PW11 O40 (SiC3 H6 NH2 )2 PtCl2 ] (abbreviated as PtII -PW11 ) for inhibiting Aβ42 aggregation. The mechanism of inhibition on Aβ42 aggregation by PtII -PW11 was attributed to the multiple interactions of PtII -PW11 with Aβ42 including coordination interaction of Pt2+ in PtII -PW11 with amino group in Aβ42 , electrostatic attraction, hydrogen bonding and van der Waals force. In cell-based assay, PtII -PW11 displayed remarkable neuroprotective effect for Aβ42 aggregation-induced cytotoxicity, leading to increase of cell viability from 49 % to 67 % at a dosage of 8 μm. More importantly, the PtII -PW11 greatly reduced Aβ deposition and rescued memory loss in APP/PS1 transgenic AD model mice without noticeable cytotoxicity, demonstrating its potential as drugs for AD treatment.
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