The aggregation behavior of the
amyloid peptide Aβ(1-28) and the
prion peptide PrP(185-208) - both responsible for
neurodegenerative disorders - was analyzed in the absence and in the presence of
poly(propylene imine) (PPI)
dendrimers at generation 5 (G5) with a dense shell of
maltose and
maltotriose units.
Thioflavin T (ThT) fluorescence assay and circular dichroism (CD) experiments indicated that fibril formation is enhanced at low
dendrimer concentration, while it is prevented at relatively high
dendrimer concentrations. Computer aided EPR analysis by means of the selected spin probe 4-octyl-dimethylammonium,2,2,6,6-tetramethyl-piperidine-1-oxyl
bromide (CAT8) further demonstrated this behavior, but also provided detailed information on the mechanism of fibril formation and on the different behavior of the differently decorated
dendrimers. The CAT8 radicals were progressively trapped at the
peptide interphase when
peptide aggregates were formed, also monitoring pre-fibrillar structures. At later time, a phase separation of the CAT8 radicals monitors the formation of further supramolecular structures where the probes become squeezed among fibrillar aggregates. The addition of small amounts of
dendrimers promotes the formation of
peptide fibrils breaking them and providing a larger amount of ends that serve as sites of replications. Conversely, a high amount of
dendrimers allows the
peptides to well separate from each other such preventing their aggregation. EPR results also indicate that the perturbation played by PPI(G5)-Maltose are more effective onto PrP(185-208) than onto Aβ(1-28), while PPI(G5)-Maltotriose is less effective towards PrP(185-208) in both promoting aggregation and preventing it by changing the
dendrimer concentration. These results provide useful information about the mechanism and interactions which regulate the ability of macromolecules like the
dendrimers to favor, prevent or cure
neurodegenerative diseases.