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
Gregori, M., Taylor, M., Salvati, E., Re, F., Mancini, S., Balducci, C., et al. (2017). Retro-inverso peptide inhibitor nanoparticles as potent inhibitors of aggregation of the Alzheimer's Aβ peptide. NANOMEDICINE, 13(2), 723-732 [10.1016/j.nano.2016.10.006].
Citazione: | Gregori, M., Taylor, M., Salvati, E., Re, F., Mancini, S., Balducci, C., et al. (2017). Retro-inverso peptide inhibitor nanoparticles as potent inhibitors of aggregation of the Alzheimer's Aβ peptide. NANOMEDICINE, 13(2), 723-732 [10.1016/j.nano.2016.10.006]. | |
Tipo: | Articolo in rivista - Articolo scientifico | |
Carattere della pubblicazione: | Scientifica | |
Presenza di un coautore afferente ad Istituzioni straniere: | Si | |
Titolo: | Retro-inverso peptide inhibitor nanoparticles as potent inhibitors of aggregation of the Alzheimer's Aβ peptide | |
Autori: | Gregori, M; Taylor, M; Salvati, E; Re, F; Mancini, S; Balducci, C; Forloni, G; Zambelli, V; Sesana, S; Michael, M; Michail, C; Tinker-Mill, C; Kolosov, O; Scherer, M; Harris, S; Fullwood, N; Masserini, M; Allsop, D | |
Autori: | GREGORI, MARIA (Primo) MASSERINI, MASSIMO ERNESTO (Penultimo) | |
Data di pubblicazione: | 2017 | |
Lingua: | English | |
Rivista: | NANOMEDICINE | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.nano.2016.10.006 | |
Appare nelle tipologie: | 01 - Articolo su rivista |
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