Does polysaccharide glycogen behave as a promoter of amyloid fibril formation at physiologically relevant concentrations?

We investigated the influence of glycogen (GG), phytoglycogen (PG), mannan (MAN) and cinnamoyl-modified GG (GG-CIN) on amyloid fibril formation. We used hen egg-white lysozyme (HEWL) as a model system and amyloid beta peptide (1-42) (Aß1-42) as an Alzheimer's disease-relevant system. For brief detection of fibrils was used thioflavin T (ThT) fluorescence assay and the results were confirmed by transmission electron microscopy (TEM). We also deal with the interaction of polysaccharides and HEWL with isothermal titration calorimetry (ITC) and dynamic light scattering (DLS). We found that all polysaccharides accelerated the formation of amyloid fibrils from both HEWL and Aß1-42. At high but physiologically relevant concentrations of GG, amyloid fibril formation was extremely accelerated for HEWL. Therefore, on the basis of the herein presented in vitro data, we hypothesize, that dietary d-glucose intake may influence amyloid fibril formation not only by influencing regulatory pathways, but also by direct glycogen-amyloid precursor protein molecular interaction, as glycogen levels in tissues are highly dependent on d-glucose intake.

Chemically modified glycogens: how they influence formation of amyloid fibrils?

The formation of amyloid fibrils from certain proteins stays behind a number of pathologies, so-called amyloidoses. Glycosaminoglycans are polysaccharides and are known natural constituents of amyloids in vivo. However, little is known about the effect of other naturally abundant polysaccharides, and even less is known about the effect of chemically modified polysaccharides on the formation of amyloid fibrils. In the case of low-molecular weight compounds, aromatic substances are known to often influence amyloid formation significantly. We investigated the influence of glycogen (GG) and several modifications of GG with cinnamoyl groups, benzoyl groups and phenylacetyl groups. As model systems, hen egg-white lysozyme (HEWL) and amyloid beta peptide (1-42) (Aß1-42), which is an Alzheimer disease-relevant system, were used. The fluorescence of thioflavin-T (ThT) was used for the rapid detection of fibrils, and the fluorescence results were confirmed by transmission electron microscopy (TEM). Other techniques, such as isothermal titration calorimetry (ITC) and dynamic light scattering (DLS), were employed to determine the interactions between HEWL and the modifications. We achieved similar results with both model systems (HEWL and Aß1-42). We showed that π-π interactions played an important role in the process of amyloid fibril formation because fundamental changes were observed in this process even with a very small number of groups containing an aromatic ring. It was found that almost all GG modifications accelerated the formation of amyloid fibrils in both model systems, HEWL and Aß1-42, except for GG-Ph1 (1.6 mol% phenylacetyl groups), which had a retarding effect compared to all other modifications.