Organoplatinum‐Substituted Polyoxometalate Inhibits β‐amyloid Aggregation for Alzheimer's Therapy
| Autor: | Wanhai Xu, Hui Wang, Jinyuan Ni, Fanjiao Zhu, Kaiwei Wan, Ke-Xin Li, Xinghua Shi, Tiedong Sun, Nannan Zheng, Qiang Peng, Jing Ai, Jia Jiao, Jichao Ma, Jing Zhao, Shaoqin Liu, Tianchan Li |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Organoplatinum Compounds Transgene Static Electricity Mice Transgenic 010402 general chemistry 01 natural sciences Neuroprotection Catalysis Microscopy Electron Transmission Alzheimer Disease β amyloid Animals Humans Cognitive Dysfunction Viability assay Maze Learning Cytotoxicity Organoplatinum Amyloid beta-Peptides 010405 organic chemistry Chemistry Hydrogen bond Circular Dichroism General Chemistry General Medicine Tungsten Compounds 0104 chemical sciences Mice Inbred C57BL Disease Models Animal Polyoxometalate Biophysics |
| Zdroj: | Angewandte Chemie. 131:18200-18207 |
| ISSN: | 1521-3757 0044-8249 |
| DOI: | 10.1002/ange.201910521 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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