Poly-L-lysine dissolves fibrillar aggregation of the Alzheimer β-amyloid peptide in vitro

被引:20
作者
Nguyen, KV
Gendrault, JL
Wolff, CM
机构
[1] Div Cellulaire & Dev, Lab Mecanismes Mol, CNRS, FRE 2168, F-67084 Strasbourg, France
[2] Univ Strasbourg 1, Fac Med, Inst Virol, F-67000 Strasbourg, France
关键词
Alzheimer's disease; preformed beta-amyloid fibrils; polyethylene glycol; poly-L-lysine; L-lysine;
D O I
10.1006/bbrc.2002.6514
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
beta-Amyloid peptide (betaA) is a major fibrillar component of neuritic plaques in Alzheimer's disease (AD) brains and is related to the pathogenesis of the disease. In this study, using electron microscopy, we describe herein the results concerning the efficacy of compounds that can dissolve preformed betaA fibrils in vitro. For such a purpose, two hydrosoluble and biocompatible polymers such as polyethylene glycol and poly-L-lysine were used. The poly-L-lysine appears as a potent dissolver of preformed betaA fibrils in vitro. Its efficiency is instantaneous. Poly-L-lysine can be used as a universal dissolver of all types of oligomeric beta-sheet conformation, precursor of the fibrils. This finding provides the basis for future investigation of the therapeutic potential Of poly-L-lysine in terms of preventing and/or retarding amyloidogenesis in AD and other types of amyloid-related disorders. (C) 2002 Elevier Science (USA).
引用
收藏
页码:764 / 768
页数:5
相关论文
共 15 条
[1]   SOLUTION CONFORMATIONS AND AGGREGATIONAL PROPERTIES OF SYNTHETIC AMYLOID BETA-PEPTIDES OF ALZHEIMERS-DISEASE - ANALYSIS OF CIRCULAR-DICHROISM SPECTRA [J].
BARROW, CJ ;
YASUDA, A ;
KENNY, PTM ;
ZAGORSKI, MG .
JOURNAL OF MOLECULAR BIOLOGY, 1992, 225 (04) :1075-1093
[2]   RELEASE OF EXCESS AMYLOID BETA-PROTEIN FROM A MUTANT AMYLOID BETA-PROTEIN PRECURSOR [J].
CAI, XD ;
GOLDE, TE ;
YOUNKIN, SG .
SCIENCE, 1993, 259 (5094) :514-516
[3]   ALZHEIMERS-DISEASE - INITIAL REPORT OF THE PURIFICATION AND CHARACTERIZATION OF A NOVEL CEREBROVASCULAR AMYLOID PROTEIN [J].
GLENNER, GG ;
WONG, CW .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1984, 120 (03) :885-890
[4]   CHARACTERIZATION AND CHROMOSOMAL LOCALIZATION OF A CDNA-ENCODING BRAIN AMYLOID OF ALZHEIMERS-DISEASE [J].
GOLDGABER, D ;
LERMAN, MI ;
MCBRIDE, OW ;
SAFFIOTTI, U ;
GAJDUSEK, DC .
SCIENCE, 1987, 235 (4791) :877-880
[5]   SUBSTITUTIONS OF HYDROPHOBIC AMINO-ACIDS REDUCE THE AMYLOIDOGENICITY OF ALZHEIMERS-DISEASE BETA-A4 PEPTIDES [J].
HILBICH, C ;
KISTERSWOIKE, B ;
REED, J ;
MASTERS, CL ;
BEYREUTHER, K .
JOURNAL OF MOLECULAR BIOLOGY, 1992, 228 (02) :460-473
[6]   Correlative memory deficits, A beta elevation, and amyloid plaques in transgenic mice [J].
Hsiao, K ;
Chapman, P ;
Nilsen, S ;
Eckman, C ;
Harigaya, Y ;
Younkin, S ;
Yang, FS ;
Cole, G .
SCIENCE, 1996, 274 (5284) :99-102
[7]   THE POSSIBLE CONTRIBUTION OF MICROGLIA AND MACROPHAGES TO DELAYED NEURONAL DEATH AFTER ISCHEMIA [J].
LEES, GJ .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1993, 114 (02) :119-122
[8]   REVERSIBLE INVITRO GROWTH OF ALZHEIMER-DISEASE BETA-AMYLOID PLAQUES BY DEPOSITION OF LABELED AMYLOID PEPTIDE [J].
MAGGIO, JE ;
STIMSON, ER ;
GHILARDI, JR ;
ALLEN, CJ ;
DAHL, CE ;
WHITCOMB, DC ;
VIGNA, SR ;
VINTERS, HV ;
LABENSKI, ME ;
MANTYH, PW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (12) :5462-5466
[9]   β-peptide immunization -: A possible new treatment for Alzheimer disease [J].
Schenk, DB ;
Seubert, P ;
Lieberburg, I ;
Wallace, J .
ARCHIVES OF NEUROLOGY, 2000, 57 (07) :934-936
[10]   Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease [J].
Scheuner, D ;
Eckman, C ;
Jensen, M ;
Song, X ;
Citron, M ;
Suzuki, N ;
Bird, TD ;
Hardy, J ;
Hutton, M ;
Kukull, W ;
Larson, E ;
LevyLahad, E ;
Viitanen, M ;
Peskind, E ;
Poorkaj, P ;
Schellenberg, G ;
Tanzi, R ;
Wasco, W ;
Lannfelt, L ;
Selkoe, D ;
Younkin, S .
NATURE MEDICINE, 1996, 2 (08) :864-870