超分子化学
淀粉样蛋白(真菌学)
灵活性(工程)
神经炎症
纳米技术
材料科学
组合化学
神经科学
生物物理学
计算生物学
疾病
化学
分子
生物
医学
有机化学
统计
病理
无机化学
数学
作者
Wen‐Bo Li,Linlin Xu,Si‐Lei Wang,Ying‐Yue Wang,Yuchen Pan,Linqi Shi,Dong‐Sheng Guo
标识
DOI:10.1002/adma.202401918
摘要
Abstract The complex pathologies in Alzheimer's disease (AD) severely limits the effectiveness of single‐target pharmic interventions, thus necessitating multi‐pronged therapeutic strategies. While flexibility is essentially demanded in constructing such multi‐target systems, for achieving optimal synergies and also accommodating the inherent heterogeneity within AD. Utilizing the dynamic reversibility of supramolecular strategy for conferring sufficient tunability in component substitution and proportion adjustment, amphiphilic calixarenes are poised to be a privileged molecular tool for facilely achieving function integration. Herein, taking β‐amyloid (Aβ) fibrillation and oxidative stress as model combination pattern, we proposed a supramolecular multifunctional integration by co‐assembling guanidinium‐modified calixarene with ascorbyl palmitate and loading dipotassium phytate within calixarene cavity. Serial pivotal events can be simultaneously addressed by this versatile system, including (1) inhibition of Aβ production and aggregation, (2) disintegration of Aβ fibrils, (3) acceleration of Aβ metabolic clearance, and (4) regulation of oxidative stress, which is verified to significantly ameliorate the cognitive impairment of 5×FAD mice, with reduced Aβ plaque content, neuroinflammation and neuronal apoptosis. Confronted with the extremely intricate clinical realities of AD, the strategy presented here exhibits ample adaptability for necessary alterations on combinations, thereby may immensely expedite the advancement of AD combinational therapy through providing an exceptionally convenient platform. This article is protected by copyright. All rights reserved
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