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].

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

GREGORI, MARIA
Primo
;
SALVATI, ELISA;RE, FRANCESCA;MANCINI, SIMONA;ZAMBELLI, VANESSA;SESANA, MARIA SILVIA;MASSERINI, MASSIMO ERNESTO
Penultimo
;
2017

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
Articolo in rivista - Articolo scientifico
Alzheimer's disease; Liposomes; Oligomer; Retro-inverso peptide; β-amyloid
English
2017
13
2
723
732
reserved
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].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/135014
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