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Recognition and Removal of Amyloid‐β by a Heteromultivalent Macrocyclic Coassembly: A Potential Strategy for the Treatment of Alzheimer's Disease
Author(s) -
Wang Hui,
Xu XinXin,
Pan YuChen,
Yan YuXing,
Hu XinYue,
Chen RunWen,
Ravoo Bart Jan,
Guo DongSheng,
Zhang Tao
Publication year - 2021
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.202006483
Subject(s) - amyloid (mycology) , neuroscience , materials science , medicine , biology , pathology
The imbalance of amyloid‐β (Aβ) production and clearance causes aggregation of Aβ 1‐42 monomers to form fibrils and amyloid plaques, which is an indispensable process in the pathogenesis of Alzheimer's disease (AD), and eventually leads to pathological changes and cognitive impairment. Consequently, Aβ 1‐42 is the most important target for the treatment of AD. However, developing a single treatment method that can recognize Aβ 1‐42 , inhibit Aβ 1‐42 fibrillation, eliminate amyloid plaques, improve cognitive impairments, and alleviate AD‐like pathology is challenging. Here, a coassembly composed of cyclodextrin (CD) and calixarene (CA) is designed, and it is used as an anti‐Aβ therapy agent. The CD–CA coassembly is based on the previously reported heteromultivalent recognition strategy and is able to successfully eliminate amyloid plaques and degrade Aβ 1‐42 monomers in 5xFAD mice. More importantly, the coassembly improves recognition and spatial cognition deficits, and synaptic plasticity impairment in the 5xFAD mice. In addition, the coassembly ameliorates AD‐like pathology including prevention of neuronal apoptosis and oxidant stress, and alteration of M1/M2 microglial polarization states. This supramolecular approach makes full use of both molecular recognition and self‐assembly of macrocyclic amphiphiles, and is a promising novel strategy for AD treatment.