Department of Chemistry, College of Natural Science, Sookmyung Women's University, Seoul 04310, Republic of Korea; Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
Biochim Biophys Acta Gen Subj. 2019 Jan;1863(1):73-81. doi: 10.1016/j.bbagen.2018.09.025. Epub 2018 Sep 29.
The small presynaptic protein α-synuclein (α-syn) is involved in the etiology of Parkinson's disease owing to its abnormal misfolding. To date, little information is known on the role of DNA nanostructures in the formation of α-syn amyloid fibrils. Here, the effects of DNA tetrahedrons on the formation of α-syn amyloid fibrils were investigated using various biochemical and biophysical methods such as thioflavin T fluorescence assay, atomic force microscopy, light scattering, transmission electron microscopy, and cell-based cytotoxicity assay. It has been shown that DNA tetrahedrons decreased the level of oligomers and increased the level of amyloid fibrils, which corresponded to decreased cellular toxicity. The ability of DNA tetrahedron to facilitate the formation of α-syn amyloid fibrils demonstrated that structured nucleic acids such as DNA tetrahedrons could modulate the process of amyloid fibril formation. Our study suggests that DNA tetrahedrons could be used as an important facilitator toward amyloid fibril formation of α-synuclein, which may be of significance in finding therapeutic approaches to Parkinson's disease and related synucleinopathies.
小的突触前蛋白α-突触核蛋白（α-syn）由于其异常错误折叠而参与帕金森病的病因。迄今为止，关于 DNA 纳米结构在α-突触核蛋白淀粉样纤维形成中的作用知之甚少。在这里，使用各种生化和生物物理方法，如硫黄素 T 荧光测定法、原子力显微镜、光散射、透射电子显微镜和基于细胞的细胞毒性测定法，研究了 DNA 四面体对α-突触核蛋白淀粉样纤维形成的影响。结果表明，DNA 四面体降低了寡聚物的水平，增加了淀粉样纤维的水平，这对应于细胞毒性的降低。DNA 四面体促进α-突触核蛋白淀粉样纤维形成的能力表明，诸如 DNA 四面体的结构化核酸可以调节淀粉样纤维形成过程。我们的研究表明，DNA 四面体可以作为α-突触核蛋白淀粉样纤维形成的重要促进剂，这对于寻找治疗帕金森病和相关突触核蛋白病的方法可能具有重要意义。
