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20241217233311.0 |
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cr uuu---uuuuu |
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241217s2024 xx |||||o 00| ||eng c |
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7 |
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|a 10.1002/adma.202413614
|2 doi
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|a pubmed24n1634.xml
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|a (DE-627)NLM381729028
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|a (NLM)39686827
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|a DE-627
|b ger
|c DE-627
|e rakwb
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|a eng
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| 100 |
1 |
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|a Meng, Ran
|e verfasserin
|4 aut
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| 245 |
1 |
0 |
|a Polyphenol Mediated Assembly
|b Tailored Nano-Dredger Unblocks Axonal Autophagosomes Retrograde Transport Traffic Jam for Accelerated Alzheimer's Waste Clearance
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|c 2024
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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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 Clear-cut evidence has linked defective autophagy to Alzheimer's disease (AD). Recent studies underscore a unique hurdle in AD neuronal autophagy: impaired retrograde axonal transport of autophagosomes, potent enough to induce autophagic stress and neurodegeneration. Nonetheless, pertinent therapy is unavailable. Here, a novel combinational therapy composed of siROCK2 and lithospermic acid B (LA) is introduced, tailored to dredge blocked axonal autophagy by multi-mitigating microtubule disruption, ATP depletion, oxidative stress, and autophagy initiation impediments in AD. Leveraging the recent discovery of multi-interactions between polyphenol LA and siRNA, ε-Poly-L-lysine, and anionic lipid nanovacuoles, LA and siROCK2 are successfully co-loaded into a fresh nano-drug delivery system, LIPPL-LA/siRC, via a ratio-flexible and straightforward fabrication process. Further modification with the TPL peptide onto LIP@PL-LA/siRC creates a brain-neuron targeted, biocompatible, and pluripotent nanomedicine, named "Nano-dredger" (T-LIP@PL-LA/siRC). Nano-dredger efficiently accelerates axonal retrograde transport and lysosomal degradation of autophagosomes, thereby facilitating the clearance of neurotoxic proteins, improving neuronal complexity, and alleviating memory defects in 3×Tg-AD transgenic mice. This study provides a fresh and flexible polyphenol/siRNA co-delivery paradigm and furnishes conceptual proof that dredging axonal autophagy represents a promising AD therapeutic avenue
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|a Journal Article
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|a alzheimer's disease
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| 650 |
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4 |
|a axonal retrograde transport
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| 650 |
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4 |
|a neuronal autophagy
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| 650 |
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4 |
|a polyphenol/siRNA co‐delivery
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| 650 |
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4 |
|a supramolecular assembly
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| 700 |
1 |
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|a Li, Yixian
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yang, Xiyu
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Cheng, Yunlong
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Xu, Minjun
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Zhou, LingLing
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Wu, Chengqin
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yu, Shuai
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Huang, Wenyi
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Wang, Tianying
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Zhang, Qizhi
|e verfasserin
|4 aut
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| 773 |
0 |
8 |
|i Enthalten in
|t Advanced materials (Deerfield Beach, Fla.)
|d 1998
|g (2024) vom: 17. Dez., Seite e2413614
|w (DE-627)NLM098206397
|x 1521-4095
|7 nnns
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| 773 |
1 |
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|g year:2024
|g day:17
|g month:12
|g pages:e2413614
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| 856 |
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|u http://dx.doi.org/10.1002/adma.202413614
|3 Volltext
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|j 2024
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