Vitamin A exhibits potent antiamyloidogenic and fibril-destabilizing effects in vitro
Vitamin A exhibits potent antiamyloidogenic and fibril-destabilizing effects in vitro
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DOI：
10.1016/j.expneurol.2004.05.035
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发表时间：
2004-10-01
影响因子：
5.3
通讯作者：
Yamada, M
中科院分区：
文献类型：
--
作者：
Ono, K;Yoshiike, Y;Yamada, M
淀粉样多肽(Abeta)在大脑中的沉积是阿尔茨海默病(AD)的一个不变特征。据报道，AD患者血浆或脑脊液中抗氧化维生素和类胡萝卜素的浓度较低，如维生素A、C、E和β-胡萝卜素，这些维生素已被临床证明可以减缓痴呆症的进展。在这项研究中，我们使用硫代黄素T(THT)的荧光光谱和电子显微镜来研究维生素A(视黄醇、视黄酸和视黄酸)、β-胡萝卜素以及维生素B2、B6、C和E在体外对β-淀粉样蛋白纤维(FAbeta)的形成、延伸和失稳的影响。其中，维生素A和β-胡萝卜素呈剂量依赖性地抑制新鲜Abeta的形成及其延伸。此外，它们还呈剂量依赖性地破坏预制的fAbetas的稳定性。所研究的分子的总体活性顺序为视黄醇=视黄酸；β-胡萝卜素。虽然确切的机制尚不清楚，但维生素A和β-胡萝卜素可能是预防和治疗阿尔茨海默病的关键分子。(C)2004 Elsevier Inc.保留所有权利。
Cerebral deposition of amyloid-peptide (Abeta) in the brain is an invariant feature of Alzheimer disease (AD). Plasma or cerebrospinal fluid concentrations of antioxidant vitamins and carotenoids, such as vitamins A, C, E, and beta-carotene, have been reported to be lower in AD patients, and these vitamins clinically have been demonstrated to slow the progression of dementia. In this study, we used fluorescence spectroscopy with thioflavin T (ThT) and electron microscopy to examine the effects of vitamin A (retinol, retinal, and retinoic acid), beta-carotene, and vitamins B2, B6, C, and E on the formation, extension, and destabilization of beta-amyloid fibrils (fAbeta) in vitro. Among them, vitamin A and beta-carotene dose-dependently inhibited formation of fAbeta from fresh Abeta, as well as their extension. Moreover, they dose-dependently destabilized preformed fAbetas. The overall activity of the molecules examined was in the order of retinol = retinal > beta-carotene > retinoic acid. Although the exact mechanisms are still unclear, vitamins A and beta-carotene could be key molecules for the prevention and therapy of AD. (C) 2004 Elsevier Inc. All rights reserved.