β-amyloid aggregation induced by human acetylcholinesterase:: inhibition studies

被引：528

作者：

Bartolini, M ^{[1
]}

Bertucci, C ^{[1
]}

Cavrini, V ^{[1
]}

Andrisano, V ^{[1
]}

机构：

[1] Univ Bologna, Dipartimento Sci Farmaceut, I-40126 Bologna, Italy

来源：

BIOCHEMICAL PHARMACOLOGY | 2003年 / 65卷 / 03期

关键词：

beta-Amyloid (1-40); human recombinant acetylcholinesterase fibrillogenesis; Alzheimer's disease; acetylcholinesterase inhibitors; mechanism of action;

D O I：

10.1016/S0006-2952(02)01514-9

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The aggregation of beta-amyloid (1-40) (Abeta) induced by human recombinant acetylcholinesterase (HuAChE) was studied by means of circular dichroism (CD) and by thioflavin T fluorescence spectroscopy. Abeta was incubated alone and with HuAChE. The kinetic of fibrils formation was followed for 48 hr. The increasing beta-conformation content induced by HuAChE, preliminary to the formation of Abeta fibrils, was determined by circular dichroism. This phenomenon was found to be related to the thioflavin T emission of fluorescence at 490 nm. Incubation experiments were performed in the presence of known AChE inhibitors (physostigmine, edrophonium, decamethonium, propidium) and drugs used for Alzheimer's disease (AD) (tacrine, donepezil), to test their capability of preventing the HuAChE-induced Abeta aggregation. The non-competitive or mixed mode of AChE inhibition was confirmed to be an essential feature. At 100 muM propidium, decamethonium, donepezil and physostigmine were found to inhibit the HuAChE-induced Abeta aggregation by 82, 25, 22 and 30%, respectively. (C) 2002 Elsevier Science Inc. All rights reserved.

引用

页码：407 / 416

页数：10

共 42 条

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