Lysosome-Targeting Protein Degradation Through Endocytosis Pathway Triggered by Polyvalent Nano-Chimera for AD Therapy

Bibliographische Detailangaben
Veröffentlicht in:	Advanced materials (Deerfield Beach, Fla.). - 1998. - (2024) vom: 17. Dez., Seite e2411061
1. Verfasser:	Wang, Xiaorong (VerfasserIn)
Weitere Verfasser:	Chen, Shiqin, Xia, Xue, Du, Yufan, Wei, Ya, Yang, Wenqin, Zhang, Yiwei, Song, Yujun, Lei, Ting, Huang, Qianqian, Gao, Huile
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2024
Zugriff auf das übergeordnete Werk:	Advanced materials (Deerfield Beach, Fla.)
Schlagworte:	Journal Article Alzheimer's disease BBB repairment lysosome‐targeting protein degradation nano‐delivery system polyvalent binding

Beschreibung
Zusammenfassung:	© 2024 Wiley‐VCH GmbH. The excessive up-regulation of receptor for advanced glycation end products (RAGE), a well-known pathological marker, drives the onset and progression of Alzheimer's disease. Although lysosome-targeting protein degradation has emerged as an effective therapeutic modality, the limited lysosome-sorting efficacy greatly hindered the degradation efficiency of target proteins. Herein, a lysosome-shuttle-like nano-chimera (endoTAC) is proposed based on polyvalent receptor binding mode for enhanced RAGE degradation as well as precise drug delivery. The endoTAC shows a high affinity to RAGE and enhances RAGE degradation due to its polyvalent-interaction with RAGE. Additionally, endoTAC features increased accumulation in diseased brain and shows promise as a precise brain delivery system. After loading with simvastatin, the SVendoTAC proves to successfully reverse pathological features both in vitro and in vivo. The work proposes that the combination of a lysosome-targeting chimera and an effective drug delivery system can be promising in Alzheimer's disease therapy
Beschreibung:	Date Revised 17.12.2024 published: Print-Electronic Citation Status Publisher
ISSN:	1521-4095
DOI:	10.1002/adma.202411061