Departamento de Nutrición y Bromatología, Toxicología y Medicina Legal, Área de Nutrición y Bromatología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
ISVV, Unité de Recherche Oenologie, Université de Bordeaux, Villenave d'Ornon, France.
Mol Nutr Food Res. 2018 Feb;62(3). doi: 10.1002/mnfr.201700383. Epub 2018 Jan 4.
Amyloid-β peptide is the main component of senile plaques in Alzheimer's disease. The inhibition of amyloid-β peptide assembly, the destabilization of amyloid-β peptide aggregates, and the decrease of its cytotoxicity for the prevention of neuronal death are considered neuroprotective effects. In this work, the protective effects against amyloid-β peptide aggregation and cytotoxicity of eight indolic compounds are evaluated: tryptophan, tryptamine, serotonin, tryptophol, N-acetylserotonin, 3-indoleacetic acid, tryptophan ethyl ester, and melatonin.
Thioflavin T spectroscopic assay, transmission electron microscopy, western blotting, circular dichroism, NMR, cell viability (thiazolyl blue tetrazolium bromide assay), quantitative PCR, and heme oxygenase activity are used. Serotonin is the most effective compound for inhibiting amyloid-β peptide aggregation. Almost all the indolic compounds tested prevent amyloid-β peptide-induced and increase cell viability, being between 9 and 25%. Melatonin and serotonin are the most active. Moreover, serotonin increased the expression of SIRT-1 and 2, heat shock protein 70, and heme oxygenase activity, this being a possible mechanism underlying the observed neuroprotective effect.
Melatonin and other related indolic compounds, mainly serotonin, show an inhibitory and destabilizing effect on amyloid-β peptide fibril formation and they possess neuroprotective properties related to the vitagenes system.
β淀粉样肽是阿尔茨海默病老年斑的主要成分。抑制β淀粉样肽聚集、破坏β淀粉样肽聚集物的稳定性、降低其细胞毒性以防止神经元死亡被认为具有神经保护作用。在这项工作中，评估了八种吲哚类化合物对β淀粉样肽聚集和细胞毒性的保护作用：色氨酸、色胺、血清素、色醇、N-乙酰血清素、3-吲哚乙酸、色氨酸乙酯和褪黑素。
使用硫黄素 T 光谱分析、透射电子显微镜、western blot、圆二色性、NMR、细胞活力（噻唑蓝溴化四唑测定）、定量 PCR 和血红素加氧酶活性进行研究。血清素是抑制β淀粉样肽聚集最有效的化合物。几乎所有测试的吲哚类化合物都能预防β淀粉样肽诱导的细胞活力降低，并增加细胞活力，其范围在 9%至 25%之间。褪黑素和血清素活性最高。此外，血清素增加了 SIRT-1 和 2、热休克蛋白 70 和血红素加氧酶的表达，这可能是观察到的神经保护作用的机制。
褪黑素和其他相关的吲哚类化合物，主要是血清素，对β淀粉样肽纤维形成具有抑制和破坏作用，并且具有与 vitagenes 系统相关的神经保护特性。
