title: Retro-inverso peptide inhibitor nanoparticles as potent inhibitors of aggregation of the Alzheimer's Aβ peptide.
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 APPSWEtransgenic 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.
authors: University of Milano-Bicocca, Nanomedicine Center NANOMIB and School of Medicine and Surgery, Monza, (MB), Italy.
authors: Maria
authors: M
authors: Gregori
authors: University of Lancaster, Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster, UK.
authors: Mark
authors: M
authors: Taylor
authors: University of Milano-Bicocca, Nanomedicine Center NANOMIB and School of Medicine and Surgery, Monza, (MB), Italy.
authors: Elisa
authors: E
authors: Salvati
authors: University of Milano-Bicocca, Nanomedicine Center NANOMIB and School of Medicine and Surgery, Monza, (MB), Italy.
authors: Francesca
authors: F
authors: Re
authors: University of Milano-Bicocca, Nanomedicine Center NANOMIB and School of Medicine and Surgery, Monza, (MB), Italy.
authors: Simona
authors: S
authors: Mancini
authors: Department of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico/Mario Negri Institute for Pharmacological Research, Milan, Italy.
authors: Claudia
authors: C
authors: Balducci
authors: Department of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico/Mario Negri Institute for Pharmacological Research, Milan, Italy.
authors: Gianluigi
authors: G
authors: Forloni
authors: University of Milano-Bicocca, Nanomedicine Center NANOMIB and School of Medicine and Surgery, Monza, (MB), Italy.
authors: Vanessa
authors: V
authors: Zambelli
authors: University of Milano-Bicocca, Nanomedicine Center NANOMIB and School of Medicine and Surgery, Monza, (MB), Italy.
authors: Silvia
authors: S
authors: Sesana
authors: University of Lancaster, Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster, UK.
authors: Maria
authors: M
authors: Michael
authors: University of Lancaster, Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster, UK.
authors: Christos
authors: C
authors: Michail
authors: University of Lancaster, Department of Physics, Faculty of Science and Technology, Lancaster, UK.
authors: Claire
authors: C
authors: Tinker-Mill
authors: University of Lancaster, Department of Physics, Faculty of Science and Technology, Lancaster, UK.
authors: Oleg
authors: O
authors: Kolosov
authors: University of Lancaster, Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster, UK.
authors: Michael
authors: M
authors: Sherer
authors: Quotient Bioresearch (Rushden) Ltd, Rushden, Northamptonshire, UK.
authors: Stephen
authors: S
authors: Harris
authors: University of Lancaster, Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster, UK.
authors: Nigel J
authors: NJ
authors: Fullwood
authors: University of Milano-Bicocca, Nanomedicine Center NANOMIB and School of Medicine and Surgery, Monza, (MB), Italy.
authors: Massimo
authors: M
authors: Masserini
authors: University of Lancaster, Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster, UK. Electronic address: d.allsop@lancaster.ac.uk.
authors: David
authors: D
authors: Allsop
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology* / Q000628:therapy*; D016229:Amyloid beta-Peptides; D000818:Animals; D001812:Blood-Brain Barrier; D006801:Humans; D008081:Liposomes; D008822:Mice, Transgenic; D053758:Nanoparticles; D010446:Peptide Fragments; D014407:Tumor Cells, Cultured
chemical_list: D016229:Amyloid beta-Peptides; D008081:Liposomes; D010446:Peptide Fragments
keywords: Alzheimer's disease; Liposomes; Oligomer; Retro-inverso peptide; β-amyloid