Recently, we identified the yeast red pigment (RP), a polymer of 1-(5′-Phosphoribosyl)-5-aminoimidazole, as a novel potential anti-amyloid agent for the therapy of neurodegenerative diseases. The purpose of this study was to further validate RP for treatment of Parkinson's disease (PD) and to clarify molecular mechanisms involved in the reduction of amyloid cytotoxicity. We investigated RP effects in vivo using Saccharomyces cerevisiae and Drosophila melanogaster PD models. Western blot analysis revealed reduction in the levels of insoluble α-synuclein in both models, while soluble α-synuclein decreased only in Drosophila. In both models RP significantly reduced α-synuclein cytotoxicity, as was revealed by immunohistochemistry in Drosophila (p < 0.001, n = 27 flies per genotype/assay) and by flow cytometry in yeast (p < 0.05). Data obtained from the yeast PD model suggests that RP antitoxic effects are associated with a drop in ROS accumulation, and slower cellular transition from the early to late apoptotic stage. Using Drosophila brain tissue sections, we have demonstrated that RP helps to compensate for an α-synuclein-mediated reduction in the number of dopaminergic neurons and leads to better performance in animal climbing tests (p < 0.001, n = 120–150 flies per genotype/assay). Taken together, these results demonstrate the potential of RP for the treatment of PD, at least in model systems.

最近，我们确定了一种酵母红色素（RP），一种1-（5'-磷酸核糖基）-5-氨基咪唑的聚合物，是治疗神经退行性疾病的新型潜在抗淀粉样蛋白药物。这项研究的目的是进一步验证可用于治疗帕金森氏病（PD）的RP，并阐明减少淀粉样蛋白细胞毒性的分子机制。我们使用酿酒酵母和果蝇PD模型在体内调查了RP的影响。蛋白质印迹分析显示，两种模型中的不溶性α-突触核蛋白水平均降低，而仅在果蝇中可溶性α-突触核蛋白水平下降。在两种模型中，RP均显着降低了α-突触核蛋白的细胞毒性，免疫组织化学证实果蝇（p  <0.001， 每个基因型/分析n = 27个果蝇）并通过流式细胞仪检测酵母中的果蝇（p  <0.05）。从酵母PD模型获得的数据表明RP的抗毒性作用与ROS积累的下降以及从早期凋亡阶段到晚期凋亡阶段的较慢细胞转变有关。使用果蝇的脑组织切片，我们证明了RP有助于补偿α-突触核蛋白介导的多巴胺能神经元数量的减少，并在动物攀爬试验中表现出更好的表现（p  <0.001，n  =每个基因型120-150蝇） / assay）。综上所述，这些结果证明了至少在模型系统中，RP具有治疗PD的潜力。