Recognition and Removal of Amyloid-β by a Heteromultivalent Macrocyclic Coassembly A Potential Strategy for the Treatment of Alzheimer's Disease

Recognition and Removal of Amyloid-β by a Heteromultivalent Macrocyclic Coassembly : A Potential Strategy for the Treatment of Alzheimer's Disease

© 2020 Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 33(2021), 4 vom: 01. Jan., Seite e2006483
1. Verfasser: Wang, Hui (VerfasserIn)
Weitere Verfasser: Xu, XinXin, Pan, Yu-Chen, Yan, YuXing, Hu, Xin-Yue, Chen, RunWen, Ravoo, Bart Jan, Guo, Dong-Sheng, Zhang, Tao
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2021
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article Alzheimer's disease amyloid plaques cognition heteromultivalent recognition pathological impairment Amyloid beta-Peptides Calixarenes 130036-26-9 Cyclodextrins mehr... amyloid beta-protein (1-42) Peptide Fragments Macrocyclic Compounds
Beschreibung
Zusammenfassung:© 2020 Wiley-VCH GmbH.
The imbalance of amyloid-β (Aβ) production and clearance causes aggregation of Aβ1-42 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, Aβ1-42 is the most important target for the treatment of AD. However, developing a single treatment method that can recognize Aβ1-42 , inhibit Aβ1-42 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 Aβ1-42 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
Beschreibung:Date Completed 24.07.2024
Date Revised 27.08.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202006483