Ono Kenjiro, Yoshiike Yuji, Takashima Akihiko, Hasegawa Kazuhiro, Naiki Hironobu, Yamada Masahito
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Exp Neurol. 2004 Oct;189(2):380-92. doi: 10.1016/j.expneurol.2004.05.035.
Cerebral deposition of amyloid beta-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.
大脑中β-淀粉样肽（Aβ）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（如维生素A、C、E和β-胡萝卜素）的浓度较低，并且这些维生素在临床上已被证明可减缓痴呆症的进展。在本研究中，我们使用硫黄素T（ThT）荧光光谱法和电子显微镜来检测维生素A（视黄醇、视黄醛和视黄酸）、β-胡萝卜素以及维生素B2、B6、C和E对体外β-淀粉样蛋白原纤维（fAβ）形成、延伸和去稳定化的影响。其中，维生素A和β-胡萝卜素以剂量依赖方式抑制新鲜Aβ形成fAβ及其延伸。此外，它们以剂量依赖方式使预先形成的fAβ去稳定化。所检测分子的总体活性顺序为视黄醇 = 视黄醛 > β-胡萝卜素 > 视黄酸。尽管确切机制仍不清楚，但维生素A和β-胡萝卜素可能是预防和治疗AD的关键分子。
