St. Petersburg Branch, Vavilov Institute of General Genetics, St. Petersburg, Russian Federation.
Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg, Russian Federation.
Sci Rep. 2019 Dec 12;9(1):18983. doi: 10.1038/s41598-019-55528-6.
Amyloids are β-sheets-rich protein fibrils that cause neurodegenerative and other incurable human diseases affecting millions of people worldwide. However, a number of proteins is functional in the amyloid state in various organisms from bacteria to humans. Using an original proteomic approach, we identified a set of proteins forming amyloid-like aggregates in the brain of young healthy rats. One of them is the FXR1 protein, which is known to regulate memory and emotions. We showed that FXR1 clearly colocalizes in cortical neurons with amyloid-specific dyes Congo-Red, Thioflavines S and T. FXR1 extracted from brain by immunoprecipitation shows yellow-green birefringence after staining with Congo red. This protein forms in brain detergent-resistant amyloid oligomers and insoluble aggregates. RNA molecules that are colocalized with FXR1 in cortical neurons are insensitive to treatment with RNase A. All these data suggest that FXR1 functions in rat brain in amyloid form. The N-terminal amyloid-forming fragment of FXR1 is highly conserved across mammals. We assume that the FXR1 protein may be presented in amyloid form in brain of different species of mammals, including humans.
淀粉样蛋白是富含β-折叠的蛋白质纤维,可导致神经退行性疾病和其他无法治愈的人类疾病,影响着全球数百万人。然而,在从细菌到人类的各种生物体中,有许多蛋白质在淀粉样状态下具有功能。我们使用原创的蛋白质组学方法,在年轻健康大鼠的大脑中鉴定出了一组形成类似淀粉样的聚集物的蛋白质。其中之一是 FXR1 蛋白,它已知可调节记忆和情绪。我们表明,FXR1 与皮质神经元中的淀粉样蛋白特异性染料刚果红、硫黄素 S 和 T 明显共定位。用刚果红染色后,从大脑中免疫沉淀提取的 FXR1 显示出黄绿色双折射。该蛋白质在大脑去污剂抗性淀粉样寡聚物和不溶性聚集体中形成。与皮质神经元中的 FXR1 共定位的 RNA 分子对 RNase A 的处理不敏感。所有这些数据表明 FXR1 在大鼠大脑中以淀粉样形式发挥作用。FXR1 的 N 端淀粉样形成片段在哺乳动物中高度保守。我们假设 FXR1 蛋白可能以淀粉样形式存在于不同物种的哺乳动物大脑中,包括人类。