Analytical Method for β-Amyloid Fibrils Using CE-Laser Induced Fluorescence and Its Application to Screening for Inhibitors of β-Amyloid Protein Aggregation
Analytical Method for β-Amyloid Fibrils Using CE-Laser Induced Fluorescence and Its Application to Screening for Inhibitors of β-Amyloid Protein Aggregation
复制标题
DOI：
10.1021/ac0701482
复制
发表时间：
2007-05
影响因子：
7.4
通讯作者：
Masaru Kato;H. Kinoshita;Mitsue Enokita;Y. Hori;T. Hashimoto;T. Iwatsubo;T. Toyo′oka
中科院分区：
文献类型：
--
作者：
Masaru Kato;H. Kinoshita;Mitsue Enokita;Y. Hori;T. Hashimoto;T. Iwatsubo;T. Toyo′oka
阿尔茨海默病患者超过2000万人，如果不开发预防或治疗药物，随着老龄化社会的到来，患者数量将急剧增加。采用ce激光诱导荧光与荧光试剂硫黄酮t相结合的方法，建立了一种快速、灵敏的β-淀粉样蛋白（Aβ）聚集体分析方法，该方法可在5 min内分离两种不同的原纤维。第一个峰在~ 4分钟迁移，被认为来自于在~ 3.5分钟迁移的原纤维的前体。该方法也适用于Aβ聚集抑制剂的高通量筛选，有望成为阿尔茨海默病的有效候选治疗药物。三种化合物（道诺霉素，3-吲哚丙酸（3-IPA），褪黑激素）用于测定。这些化合物的抗聚集活性排序为道诺霉素b> 3-IPA b>褪黑素，与报道的结果一致。
More than 20 million people are suffering from Alzheimer's disease, and the number of patients will dramatically increase with the arrival of an aging society unless preventive or curative medications are discovered. A fast and sensitive analytical method for β-amyloid (Aβ) aggregates was developed by the combination of CE-laser induced fluorescence and the fluorescence reagent, thioflavine T. The developed method separates two different fibrils within 5 min. The first peak, which migrated at ∼4 min, was supposed to be derived from a precursor of a fibril that migrated at ∼3.5 min. The developed method was also applicable to the high-throughput screening of the Aβ aggregation inhibitors, which was expected to be an effective therapeutic agent candidate of Alzheimer's disease. Three compounds (daunomycin, 3-indolepropionic acid (3-IPA), melatonin) were used for the assay. The order of the antiaggregation activity of these compounds was daunomycin > 3-IPA > melatonin, which was the same as that of the repor...