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  • Nanomedicine (in press)

    Rights statement: This is the author’s version of a work that was accepted for publication in Nanomedicine. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Nanomedicine, 13, 2, 2017 DOI: 10.1016/j.nano.2016.10.006

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Retro-inverso peptide inhibitor nanoparticles as potent inhibitors of aggregation of the Alzheimer’s Aβ peptide

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<mark>Journal publication date</mark>02/2017
<mark>Journal</mark>Nanomedicine: Nanotechnology, Biology, and Medicine
Issue number2
Volume13
Number of pages10
Pages (from-to)723-732
Publication StatusPublished
Early online date19/10/16
<mark>Original language</mark>English

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/BL6 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.

Bibliographic note

This is the author’s version of a work that was accepted for publication in Nanomedicine. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Nanomedicine, 13, 2, 2017 DOI: 10.1016/j.nano.2016.10.006