Copper- and iron-induced differential fibril formation in α-synuclein: TEM study

α-Synuclein filaments are the central component of intracytoplasmic inclusion bodies characteristic of Parkinson's disease (PD) and related disorders. Metals are the significant etiological factors in PD, and their interaction with α-synuclein affect dramatically the kinetics of fibrillation. Currently, we have investigated the influence of Cu(II) and Fe(III) on α-synuclein fibril formation. Cu(II) and Fe(III) selectively and differentially induced the formation of discrete α-synuclein fibrillar species. Transmission electron microscopy was used to monitor the aggregation state of α-synuclein (wild-type, A30P, A53T, and E46K) after 60 h with stirring at 37 °C in the presence and absence of metal ions. Cu(II) has induced thin long network-like fibrils with the wild-type of α-synuclein, while the mutant, showed amorphous aggregates with no fibrillar forms. Fe(III) induced short and thick fibrils with both wild and mutant forms and were similar to α-synuclein fibrils incubated without metal ion. The present study illustrates the metal-specific fibril morphology, and has relevance in understanding the role of metals in neurodegeneration.