Modulating alpha-synuclein fibril formation using DNA tetrahedron nanostructures

Abstract

The small presynaptic protein alpha-synuclein (alpha-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 alpha-syn amyloid fibrils. Here, the effects of DNA tetrahedrons on the formation of alpha-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 alpha-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 alpha-synuclein, which may be of significance in finding therapeutic approaches to Parkinson's disease and related synucleinopathies.