GM1 and OligoGM1 Drive Divergent α-Synuclein Aggregation Pathways.
Cecilia Vasti1,2, María Elisa Mariani3,4, Mónica S Sánchez5,6
1Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Fisicoquímica, Córdoba X5000HUA, Argentina.
Langmuir : the ACS Journal of Surfaces and Colloids
|December 13, 2025
Summary
The lipid portion of GM1 ganglioside inhibits alpha-synuclein aggregation, promoting toxic oligomers in Parkinson's disease research. The oligosaccharide alone accelerates fibrillation, highlighting GM1's complex role.
Area of Science:
- Neuroscience
- Biochemistry
- Biophysics
Background:
- Parkinson's disease (PD) involves alpha-synuclein (AS) amyloid deposits.
- AS fibrillation forms toxic oligomers and mature fibrils.
- GM1 ganglioside inhibits AS fibrillation.
Purpose of the Study:
- Investigate the effect of GM1's oligosaccharide (oligoGM1) on AS fibrillation.
- Compare oligoGM1's effect to GM1 micelles.
- Determine the role of GM1's lipid and oligosaccharide components in AS aggregation.
Main Methods:
- Synthesized oligoGM1.
- Used atomic force microscopy (AFM) and dot blotting to analyze AS species.
- Performed Thioflavin T (ThT) aggregation kinetics assays.
- Conducted cytotoxicity assays in SH-SY5Y neuroblastoma cells.
Main Results:
- oligoGM1 stimulated AS amyloid fibril formation.
- GM1 reduced or inhibited AS aggregation in a lipid/protein ratio-dependent manner.
- GM1 promoted the formation of toxic AS oligomers, while oligoGM1 accelerated fibril formation.
- Oligomers formed with GM1 were more toxic than AS fibrils.
Conclusions:
- The hydrophobic lipid moiety of GM1 is crucial for modulating AS aggregation.
- GM1's inhibition of fibrillation and promotion of toxic oligomers are key findings.
- Amyloid deposition extent may not directly correlate with neurodegenerative pathogenesis.
