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241217s2024 xx |||||o 00| ||eng c |
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|a 10.1002/adma.202411061
|2 doi
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|a pubmed24n1634.xml
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|a DE-627
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|e rakwb
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|a eng
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|a Wang, Xiaorong
|e verfasserin
|4 aut
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|a Lysosome-Targeting Protein Degradation Through Endocytosis Pathway Triggered by Polyvalent Nano-Chimera for AD Therapy
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|c 2024
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
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|2 rdamedia
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|a ƒa Online-Ressource
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|a Date Revised 17.12.2024
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|a published: Print-Electronic
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|a Citation Status Publisher
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|a © 2024 Wiley‐VCH GmbH.
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|a 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
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|a Journal Article
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|a Alzheimer's disease
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|a BBB repairment
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|a lysosome‐targeting protein degradation
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|a nano‐delivery system
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|a polyvalent binding
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|a Chen, Shiqin
|e verfasserin
|4 aut
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1 |
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|a Xia, Xue
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Du, Yufan
|e verfasserin
|4 aut
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| 700 |
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|a Wei, Ya
|e verfasserin
|4 aut
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| 700 |
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|a Yang, Wenqin
|e verfasserin
|4 aut
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| 700 |
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|a Zhang, Yiwei
|e verfasserin
|4 aut
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| 700 |
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|a Song, Yujun
|e verfasserin
|4 aut
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| 700 |
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|a Lei, Ting
|e verfasserin
|4 aut
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| 700 |
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|a Huang, Qianqian
|e verfasserin
|4 aut
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| 700 |
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|a Gao, Huile
|e verfasserin
|4 aut
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| 773 |
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|i Enthalten in
|t Advanced materials (Deerfield Beach, Fla.)
|d 1998
|g (2024) vom: 17. Dez., Seite e2411061
|w (DE-627)NLM098206397
|x 1521-4095
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|g year:2024
|g day:17
|g month:12
|g pages:e2411061
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|u http://dx.doi.org/10.1002/adma.202411061
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