Buscador de Personas - SIGEVA - Universidad Nacional de Córdoba

The aggregation of the β-amyloid protein Aβ(1-42) plays a fundamental role in the pathogenesis of Alzheimer´s disease (AD) that is closely linked to neuronal toxicity. It has been described that Aβ(1-42) interacts with gangliosides with a certain affinity. The accumulation of GM1ganglioside complexes with Aβ(1-42) has been reported in brains of patients with AD. Previous studies indicate that both the oligosaccharide portion and the hydrophobic portion of the GM1 participate in the interaction. In order to discern the participation of the oligosaccharide portion, we synthesized new molecules containing only the oligosaccharide portion of GM1 ganglioside (called osGM1) or covalently linked to chitosan, a biocompatible cationic polymer (osGM1-Ch ganglioside like-glycan cluster molecules). This nanoparticle was synthesized by using low molecular weight chitosan (MW~ 100 kD) loaded with 1 µmol osGM1/1.28 mg of chitosan. We have tested the effect of these new molecules against GM1 micelles.We used β-lactoglobulin (β-lg) as amyloid-like aggregation model. Benzyl alcohol induce amyloid fibers Thio T positive (a fluorescent marker of amyloid fibers) in β-lg in aqueous buffer at physiologic pH. We have also used synthetic Aβ(1-42) peptide. Preliminary results showed that osGM1 has no practically effect on β-lg induced, fibers, GM1 and acidic GM1-H+ micelles have a slight disaggregating effect whereas osGM1-Ch enhances its effect. Over preformed Aβ(1-42) fibers in aqueous solution, osGM1 prevents or delays the time depending self-disaggregating amyloid fibers. Instead, nanoparticle osGM1-Ch has a marked disaggregating effect over preformed Aβ(1-42) fibers but similar effect was also obtained by non-loaded carrier chitosan. Additional experiments are still necessary to attribute some property to the oligosaccharide part of the GM1 ganglioside in its aggregating-disaggregating effect in in-vitro experimental models of amyloids.

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