Abstract
Aggregation of amyloid-β peptide (Aβ) is a key event in the pathogenesis of Alzheimer's disease (AD). We investigated the effects of nanoliposomes decorated with the retro-inverso peptide RI-OR2-TAT (Ac-rGffvlkGrrrrqrrkkrGy-NH2) on the aggregation and toxicity of Aβ. Remarkably low concentrations of these peptide inhibitor nanoparticles (PINPs) were required to inhibit the formation of Aβ oligomers and fibrils in vitro, with 50% inhibition occurring at a molar ratio of ~1:2000 of liposome-bound RI-OR2-TAT to Aβ. PINPs also bound to Aβ with high affinity (Kd=13.2-50 nM), rescued SHSY-5Y cells from the toxic effect of pre-aggregated Aβ, crossed an in vitro blood-brain barrier model (hCMEC/D3 cell monolayer), entered the brains of C57 BL/6 mice, and protected against memory loss in APPSWE transgenic mice in a novel object recognition test. As the most potent aggregation inhibitor that we have tested so far, we propose to develop PINPs as a potential disease-modifying treatment for AD.
Original language | English |
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Pages (from-to) | 723-732 |
Number of pages | 10 |
Journal | Nanomedicine: Nanotechnology, Biology, and Medicine |
Volume | 13 |
Issue number | 2 |
DOIs | |
Publication status | Published - Feb 2017 |
Keywords
- Alzheimer Disease
- Amyloid beta-Peptides
- Animals
- Blood-Brain Barrier
- Humans
- Liposomes
- Mice, Transgenic
- Nanoparticles
- Peptide Fragments
- Tumor Cells, Cultured
- Journal Article