Recent literature demonstrates the accelerated aggregation of alpha-synuclein, a protein implicated in the pathogenesis of Parkinson's disease (PD), by the presence of preformed fibrillar conformers in vitro. Furthermore, these preformed fibrillar seeds are suggested to accelerate pathological induction in vivo when injected into the brains of mice. Variation in the results of in vivo studies is proposed to be caused by alpha-synuclein conformational variants. To investigate the impact of amino acid sequence on seeding efficiency, human and mouse alpha-synuclein seeds, which vary at 7 amino acid residues, were generated and cross-seeding kinetics studied. Using transmission electron microscopy (TEM), we confirmed that mouse alpha-synuclein aggregated more rapidly than human alpha-synuclein. Subsequently, we determined that seeding of human and mouse alpha-synuclein was more rapid in the presence of seeds generated from the same species. In addition, an established amyloid inhibitor, scyllo-inositol, was examined for potential inhibitory effects on alpha-synuclein aggregation. TEM analysis of protein:inhibitor assays demonstrated that scyllo-inositol inhibits the aggregation of alpha-synuclein, suggesting the therapeutic potential of the small molecule in PD. (C) 2015 Elsevier Inc. All rights reserved.