Polyphenol Mediated Assembly : Tailored Nano-Dredger Unblocks Axonal Autophagosomes Retrograde Transport Traffic Jam for Accelerated Alzheimer's Waste Clearance
© 2024 Wiley‐VCH GmbH.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - (2024) vom: 17. Dez., Seite e2413614 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2024
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| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article alzheimer's disease axonal retrograde transport neuronal autophagy polyphenol/siRNA co‐delivery supramolecular assembly |
| Zusammenfassung: | © 2024 Wiley‐VCH GmbH. 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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| Beschreibung: | Date Revised 17.12.2024 published: Print-Electronic Citation Status Publisher |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202413614 |