Parkinson’s disease (PD) is an age-related disorder characterized by thepresence of amyloid deposits of the 140-amino-acid protein AS (α-synuclein). AS fibrillation,the process of native soluble proteins misfolding into insoluble fibrilscomprising cross-β-sheets, involving transient prefibrillar species with differentbiophysical features. In vitroevidence suggests that pre-fibrillar species (oligomeric intermediates), ratherthan mature amyloid fibrils, are likely to be the primary pathogenic agents inneurodegenerative diseases.

We previouslydemonstrated that oligoGM₁ (the oligosaccharidesoluble portion of GM₁ ganglioside) stimulated the formation ofamyloid fibrils as compared to GM₁ ganglioside which reduces ASaggregation. The morphological analysis showed that AS fibrils are lower in heightin the presence of oligoGM₁ compared to AS fibrils and we visualizedstructures compatible with AS oligomers in the presence of GM₁.

In this report, by usingdot blot and atomic force microscopy (AFM), we demonstrated that GM₁stimulates the formation of oligomeric structures of AS in vitro.

Furthermore, weverified that, in the presence of GM₁, aggregation kinetics(followed by Thio T fluorescence) is lower respect to oligoGM₁.Through this analysis, we confirmed that oligoGM₁ accelerates thefibrillation of AS.

Finally, cytotoxicityassay with cell culture of human SH-SY5Y neuroblastoma cells, demonstrated thatoligomers obtained in the presence of GM₁ have a higher cytotoxicitythan AS fibers formed both in the absence or presence of oligoGM₁.

The results obtainedcontribute to the hypothesis recently emerged that demonstrate that the extentof fibrillary amyloid plaquet deposition not correlate with neurodegenerative disease pathogenesis.