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Catechol derivatives inhibit the fibril formation of amyloid-β peptides

机译:儿茶酚衍生物抑制淀粉样β肽的原纤维形成

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摘要

The inhibition of fibril formation of amyloid β proteins (Aβ) would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). Dopamine (DA) and other catechol derivatives were used as inhibitory factors for Aβ fibril formation. The fibril formation of Aβ was monitored by Thiofiavin T fluorescence, a transmission electron microscopy (TEM) and a total internal reflection fluorescence microscopy (TIRFM). Catechol and its derivatives showed the dose-dependent inhibitory effects on the spontaneous Aβ fibril formation. The inhibitory activity depended on the chemical structure of catechol derivatives both in the presence and absence of the liposome a model of biomembrane. Formation of catechol quinone-conjugated-Aβ adduct by a Schiff-base is a key step for the inhibition effect of Aβ fibril formation.
机译:淀粉样β蛋白(Aβ)的原纤维形成的抑制将是用于治疗阿尔茨海默氏病(AD)的有吸引力的治疗靶标。多巴胺(DA)和其他儿茶酚衍生物被用作Aβ原纤维形成的抑制因子。通过硫硫素T荧光,透射电子显微镜(TEM)和全内反射荧光显微镜(TIRFM)监测Aβ的原纤维形成。邻苯二酚及其衍生物对自发性Aβ原纤维形成具有剂量依赖性的抑制作用。在脂质体存在与否的情况下,抑制活性取决于儿茶酚衍生物的化学结构。通过席夫碱形成邻苯二酚醌-Aβ加合物是抑制Aβ原纤维形成的关键步骤。

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