Xanthene food dye, as a modulator of Alzheimer's disease amyloid-beta peptide aggregation and the associated impaired neuronal cell function.
Xanthene food dye, as a modulator of Alzheimer's disease amyloid-beta peptide aggregation and the associated impaired neuronal cell function.
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DOI：
10.1371/journal.pone.0025752
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kwon I
中科院分区：
文献类型：
--
作者：
Wong HE;Kwon I
阿尔茨海默病（AD）是最常见的痴呆症。阿尔茨海默病是一种退化性大脑疾病，会导致记忆、思维和行为方面的问题。淀粉样蛋白- β肽（Aβ）的聚集与阿尔茨海默病的病理发展密切相关。为了寻找安全有效的调节剂，我们评估了红素B （ER）对a β聚集和a β相关神经元细胞功能受损的调节能力。红素B是美国食品和药物管理局（FDA）批准的红色食用染料。为了评估ER对Aβ聚集的调节能力，我们采用了透射电镜（TEM）、硫黄素T （ThT）荧光测定和Aβ特异性抗体免疫测定。Aβ样品的TEM图像和ThT荧光显示，原原纤维主要生成，并持续至少3天。内质网诱导的原原纤维的平均长度与超过Aβ单体化学计量浓度的内质网浓度成反比。Aβ特异性抗体的免疫分析结果表明，ER与Aβ的n端结合并抑制淀粉样蛋白纤维的形成。为了评估Aβ相关的毒性，我们测定了在没有或存在ER的情况下形成的Aβ聚集体对SH-SY5Y神经母细胞瘤细胞的还原活性。当ER浓度高于Aβ的化学计量浓度时，细胞还原活性增加，而在500µM ER下，Aβ相关的还原活性损失可以忽略不计。我们的研究结果表明，内质网是一种新的a β聚集调节剂，可以降低a β相关的细胞功能受损。我们的研究结果还表明，杂蒽染料可能是一种新型的a β聚集小分子调节剂。由于已证实的安全性和血脑通透性，内质网是一种特别有吸引力的与神经退行性疾病相关的淀粉样蛋白聚集调节剂。
Alzheimer's disease (AD) is the most common form of dementia. AD is a degenerative brain disorder that causes problems with memory, thinking and behavior. It has been suggested that aggregation of amyloid-beta peptide (Aβ) is closely linked to the development of AD pathology. In the search for safe, effective modulators, we evaluated the modulating capabilities of erythrosine B (ER), a Food and Drug Administration (FDA)-approved red food dye, on Aβ aggregation and Aβ-associated impaired neuronal cell function. In order to evaluate the modulating ability of ER on Aβ aggregation, we employed transmission electron microscopy (TEM), thioflavin T (ThT) fluorescence assay, and immunoassays using Aβ-specific antibodies. TEM images and ThT fluorescence of Aβ samples indicate that protofibrils are predominantly generated and persist for at least 3 days. The average length of the ER-induced protofibrils is inversely proportional to the concentration of ER above the stoichiometric concentration of Aβ monomers. Immunoassay results using Aβ-specific antibodies suggest that ER binds to the N-terminus of Aβ and inhibits amyloid fibril formation. In order to evaluate Aβ-associated toxicity we determined the reducing activity of SH-SY5Y neuroblastoma cells treated with Aβ aggregates formed in the absence or in the presence of ER. As the concentration of ER increased above the stoichiometric concentration of Aβ, cellular reducing activity increased and Aβ-associated reducing activity loss was negligible at 500 µM ER. Our findings show that ER is a novel modulator of Aβ aggregation and reduces Aβ-associated impaired cell function. Our findings also suggest that xanthene dye can be a new type of small molecule modulator of Aβ aggregation. With demonstrated safety profiles and blood-brain permeability, ER represents a particularly attractive aggregation modulator for amyloidogenic proteins associated with neurodegenerative diseases.