Trehalose inhibits fibrillation of A53T mutant alpha-synuclein and disaggregates existing fibrils

The aggregation of alpha-synuclein (AS) is pivotally implicated in the development of Parkinson’s disease (PD), inhibiting this process might be effective in treating PD. Here, by using circular dichroism spectroscopy, thioflavin T fluorescence, and atomic force microscopy, we found that trehalose at low concentration disaggregates preformed A53T AS protofibrils and fibrils into small aggregates or even random coil structure, while trehalose at high concentration slows down the structural transition into β-sheet structure and completely prevents the formation of mature A53T AS fibrils. Further work in vivo will be needed to evaluate its potential as a novel strategy for treating PD.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (125 K)Download as PowerPoint slideHighlights► A53T AS undergoes an obvious fibrillation process in absence of trehalose. ► Trehalose at low concentration disassembles existent fibril into random coil. ► Trehalose at high concentration prevents self-assembly of A53T AS into fibrils.