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

被引：50

作者：

Gregori, Maria ^{[1
,2
]}

Taylor, Mark ^{[3
]}

Salvati, Elisa ^{[1
,2
]}

Re, Francesca ^{[1
,2
]}

Mancini, Simona ^{[1
,2
]}

Balducci, Claudia ^{[4
]}

Forloni, Gianluigi ^{[4
]}

Zambelli, Vanessa ^{[1
,2
]}

Sesana, Silvia ^{[1
,2
]}

Michael, Maria ^{[3
]}

Michail, Christos ^{[3
]}

Tinker-Mill, Claire ^{[5
]}

Kolosov, Oleg ^{[5
]}

Sherer, Michael ^{[3
]}

Harris, Stephen ^{[6
]}

Fullwood, Nigel J. ^{[3
]}

Masserini, Massimo ^{[1
,2
]}

Allsop, David ^{[3
]}

机构：

[1] Univ Milano Bicocca, Nanomed Ctr NANOMIB, Monza, MB, Italy

[2] Sch Med & Surg, Monza, MB, Italy

[3] Univ Lancaster, Fac Hlth & Med, Div Biomed & Life Sci, Lancaster, England

[4] Mario Negri Inst Pharmacol Res, Ist Ricovero & Cura Carattere Sci, Dept Neurosci, Milan, Italy

[5] Univ Lancaster, Fac Sci & Technol, Dept Phys, Lancaster, England

[6] Quotient Biores Rushden Ltd, Rushden, Northants, England

来源：

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE | 2017年 / 13卷 / 02期

基金：

英国工程与自然科学研究理事会;

关键词：

Alzheimer's disease; Liposomes; Retro-inverso peptide; beta-amyloid; Oligomer; BLOOD-BRAIN-BARRIER; LONG-TERM POTENTIATION; AMYLOID-BETA; DRUG TRANSPORT; IN-VITRO; BILAYER-MEMBRANES; BINDING-AFFINITY; PROTEIN; DISEASE; OLIGOMERS;

D O I：

10.1016/j.nano.2016.10.006

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Aggregation of amyloid-beta peptide (A beta) 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 Aa. Remarkably low concentrations of these peptide inhibitor nanoparticles (PINPs) were required to inhibit the formation of A beta oligomers and fibrils in vitro, with 50% inhibition occurring at a molar ratio of similar to 1: 2000 of liposome-bound RI-OR2-TAT to Aa. PINPs also bound to Aa with high affinity (Kd = 13.2-50 nM), rescued SHSY-5Y cells from the toxic effect of pre-aggregated Aa, crossed an in vitro blood-brain barrier model (hCMECD3 cellmonolayer), entered the brains of C57BL6mice, and protected againstmemory loss inAPPSWE transgenic mice in a novel object recognition test. As themost potent aggregation inhibitor that we have tested so far, we propose to develop PINPs as a potential disease-modifying treatment for AD. (C)2016 Elsevier Inc. All rights reserved.

引用

页码：723 / 732

页数：10

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