Influence of dendrimer's structure on its activity against amyloid fibril formation

被引：148

作者：

Klajnert, B. ^{[1
]}

Cortijo-Arellano, M.

Cladera, J.

Bryszewska, M.

机构：

[1] Univ Lodz, Dept Gen Biophys, PL-90131 Lodz, Poland

[2] Univ Autonoma Barcelona, Dept Biochem & Mol Biol, E-08193 Barcelona, Spain

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2006年 / 345卷 / 01期

关键词：

dendrimer; prion; Alzheimer; amyloid peptide; aggregation;

D O I：

10.1016/j.bbrc.2006.04.041

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Inhibition of fibril assembly is a potential therapeutic strategy in neurodegenerative disorders such as prion and Alzheimer's diseases. Highly branched, globular polymers-dendrimers-are novel promising inhibitors of fibril formation. In this study, the effect of polyamidoamine (PAMAM) dendrimers (generations 3rd, 4th, and 5th) on amyloid aggregation of the prion peptide PrP 185-208 and the Alzheimer's peptide A beta 1-28 was examined. Amyloid fibrils were produced in vitro and their formation was monitored using the dye thioflavin T (ThT). Fluorescence studies were complemented with electron microscopy. The results show that the higher the dendrimer generation, the larger the degree of inhibition of the amyloid aggregation process and the more effective are dendrimers in disrupting the already existing fibrils. A hypothesis on dendrimer-peptide interaction mechanism is presented based on the dendrimers' molecular structure. (c) 2006 Elsevier Inc. All rights reserved.

引用

收藏

页码：21 / 28

页数：8

相关论文

共 31 条

[21] Poly-L-lysine dissolves fibrillar aggregation of the Alzheimer β-amyloid peptide in vitro [J].

Nguyen, KV ;

Gendrault, JL ;

Wolff, CM .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 291 (04) :764-768

[22]

PATTERSON WJ, 1999, COMMUN DIS PUBLIC HL, V1, P5

[23] Inhibition by aplidine of the aggregation of the prion peptide PrP 106-126 into β-sheet fibrils [J].

Pérez, M ;

Sadqi, M ;

Muñoz, V ;

Avila, J .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2003, 1639 (02) :133-139

[24] An autocatalytic reaction, as a model for the kinetics of the aggregation of β-amyloid [J].

Sabaté, R ;

Gallardo, M ;

Estelrich, J .

BIOPOLYMERS, 2003, 71 (02) :190-195

[25] Cationic phosphorus-contain ing dendrimers reduce prion replication both in cell culture and in mice infected with scrapie [J].

Solassol, J ;

Crozet, C ;

Perrier, V ;

Leclaire, J ;

Béranger, F ;

Caminade, AM ;

Meunier, B ;

Dormont, D ;

Majoral, JP ;

Lehmann, S .

JOURNAL OF GENERAL VIROLOGY, 2004, 85 :1791-1799

[26] Elimination of prions by branched polyamines and implications for therapeutics [J].

Supattapone, S ;

Nguyen, HOB ;

Cohen, FE ;

Prusiner, SB ;

Scott, MR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (25) :14529-14534

[27] Branched polyamines cure prion-infected neuroblastoma cells [J].

Supattapone, S ;

Wille, H ;

Uyechi, L ;

Safar, J ;

Tremblay, P ;

Szoka, FC ;

Cohen, FE ;

Prusiner, SB ;

Scott, MR .

JOURNAL OF VIROLOGY, 2001, 75 (07) :3453-3461

[28] Tetracycline affects abnormal properties of synthetic PrP peptides and PrPSc in vitro [J].

Tagliavini, F ;

Forloni, G ;

Colombo, L ;

Rossi, G ;

Girola, L ;

Canciani, B ;

Angeretti, N ;

Giampaolo, L ;

Peressini, E ;

Awan, T ;

De Gioia, L ;

Ragg, E ;

Bugiani, O ;

Salmona, M .

JOURNAL OF MOLECULAR BIOLOGY, 2000, 300 (05) :1309-1322

[29] STARBURST DENDRIMERS - MOLECULAR-LEVEL CONTROL OF SIZE, SHAPE, SURFACE-CHEMISTRY, TOPOLOGY, AND FLEXIBILITY FROM ATOMS TO MACROSCOPIC MATTER [J].

TOMALIA, DA ;

NAYLOR, AM ;

GODDARD, WA .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 1990, 29 (02) :138-175

[30] Spectral properties of thioflavin T and its complexes with amyloid fibrils [J].

Voropai, E.S. ;

Samtsov, M.P. ;

Kaplevskii, K.N. ;

Maskevich, A.A. ;

Stepuro, V.I. ;

Povarova, O.I. ;

Kuznetsova, I.M. ;

Turoverov, K.K. ;

Fink, A.L. ;

Uverskii, V.N. .

Journal of Applied Spectroscopy, 2003, 70 (06) :868-874

← 1 2 3 4 →