Chen, Junyang;
(2025)
Nanomedicine modulation of endothelial low-density lipoprotein receptor-related protein 1 at the blood brain barrier for Alzheimer's disease therapy.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
This study introduces an innovative therapeutic concept for Alzheimer’s disease, which involves the use of nano multivalent scaffolds functionalized with peptides that specifically target low - density lipoprotein receptor - related protein 1 (LRP1) receptors. These scaffolds are engineered to interact with transport receptors at the blood - brain barrier. These nano multivalent platforms interact with LRP1 receptors in a highly specific manner, thereby significantly enhancing LRP1 - PACSIN2 - mediated transcytosis across the endothelial cells of the barrier. Experimental results from Alzheimer’s disease model mice demonstrate that this therapeutic approach effectively decreases amyloid - β accumulation and substantially ameliorates cognitive function. It has been demonstrated that these cognitive improvements persist throughout the remaining lifespan of the treated mice. This research introduces a novel drug design methodology combining multivalent targeting with membrane trafficking regulation, thereby establishing a unique therapeutic paradigm. Furthermore, the study underscores the blood - brain barrier’s indispensable contribution to the pathogenesis of Alzheimer’s disease and highlights the importance of LRP1 - mediated amyloid - β clearance.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Nanomedicine modulation of endothelial low-density lipoprotein receptor-related protein 1 at the blood brain barrier for Alzheimer's disease therapy |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10206182 |
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