Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran.
Biol Chem. 2020 Sep 25;401(10):1143-1151. doi: 10.1515/hsz-2019-0446.
α-Synuclein fibrillation is now regarded as a major pathogenic process in Parkinson's disease and its proteinaceous deposits are also detected in other neurological disorders including Alzheimer's disease. Therefore anti-amyloidegenic compounds may delay or prevent the progression of synucleinopathies disease. Molecular chaperones are group of proteins which mediate correct folding of proteins by preventing unsuitable interactions which may lead to aggregation. The objective of this study was to investigate the anti-amyloidogenic effect of molecular chaperone artemin on α-synuclein. As the concentration of artemin was increased up to 4 μg/ml, a decrease in fibril formation of α-synuclein was observed using thioflavin T (ThT) fluorescence and congo red (CR) assay. Transmission electron microscopy (TEM) images also demonstrated a reduction in fibrils in the presence of artemin. The secondary structure of α-synuclein was similar to its native form prior to fibrillation when incubated with artemin. A cell-based assay has shown that artemin inhibits α-synuclein aggregation and reduce cytotoxicity, apoptosis and reactive oxygen species (ROS) production. Our results revealed that artemin has efficient chaperon activity for preventing α-synuclein fibril formation and toxicity.
α-突触核蛋白纤维形成现在被认为是帕金森病的主要致病过程，其蛋白沉积物也在包括阿尔茨海默病在内的其他神经退行性疾病中被检测到。因此，抗淀粉样变化合物可能会延迟或预防突触核蛋白病的进展。分子伴侣是一组蛋白质，通过防止可能导致聚集的不合适相互作用来介导蛋白质的正确折叠。本研究的目的是研究分子伴侣 artemin 对 α-突触核蛋白的抗淀粉样变作用。当 artemin 的浓度增加到 4μg/ml 时，使用硫黄素 T（ThT）荧光和刚果红（CR）测定法观察到 α-突触核蛋白纤维形成减少。透射电子显微镜（TEM）图像也表明在 artemin 存在下纤维减少。当与 artemin 孵育时，α-突触核蛋白的二级结构与其原纤维形式相似。基于细胞的测定表明，artemin 抑制 α-突触核蛋白聚集并降低细胞毒性、细胞凋亡和活性氧（ROS）的产生。我们的结果表明，artemin 具有有效的伴侣活性，可预防 α-突触核蛋白纤维形成和毒性。
