Spontaneous formation of different forms of alpha-synuclein fibrils from a recombinant protein

Abstract

Alpha-synuclein is a protein, the conformational changes of which lead to the development of such socially significant diseases as Parkinson's disease and amyotrophic lateral sclerosis. The methods for differential diagnostics of these diseases based on the use of alpha-synuclein in a non-native conformation obtained from patients as a seed for inducing fibrillogenesis and studying the morphology of the resulting amyloid-like fibrils were described in a number of studies. The authors associate such properties of the seed with the presence of post-translational modifications in the protein obtained from patients. At the same time, the production of fibrils differing in morphology from recombinant alpha-synuclein under various conditions of fibrillogenesis is also described. In this work, we show that the formation of morphologically distinct fibril types from recombinant alpha-synuclein lacking post-translational modifications is possible under the same conditions, and that spontaneously arising different fibril types, when used as a seed for fibrillogenesis, lead to the formation of recombinant protein fibrils morphological similar to the parental seed. The results of the work can be used both in studying the fundamental mechanisms of conformation transfer and in developing test systems for synucleinopathies.