Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the aggregation of extracellular β-amyloid and the intracellular microtubule-associated protein Tau. Neurodegeneration is associated inter alia with the activation of microglial cells, neuroinflammation, oxidative stress, and diminished transduction of impulses in cholinergic neurons. Current pharmacotherapy for AD is based mainly on modulation of acetylcholine hydrolysis, administration of non-steroidal anti-inflammatory drugs and antioxidants. Novel drugs with antiamyloidic properties are currently being sought. Cationic phosphorus dendrimers have been proven to modulate amyloidogenesis and stop the aggregation of Tau protein. An ideal drug for AD should demonstrate anti-inflammatory properties, inhibit acetylcholine hydrolysis, and have antioxidant capacity. Cationic phosphorus dendrimers (generation 3 and generation 4) show the foregoing properties. They inhibit acetylcholinesterase activity, can decrease the secretion of TNF-α, and have weak antioxidant effects. The results presented suggest that phosphorus dendrimers may be considered in the future as agents in AD therapy.

Nematode Caenorhabditis elegans (C. elegans) was used to investigate the impact of silver nanoparticles (SNP), multiwalled carbon nanotubes (MWCNT), and polyamidoamine dendrimers (PAMAM) used in concentration of 10¹⁰ particle/mL. Population-based observations and gene expression analysis were employed in this study. SNP and PAMAM caused decrease in the number of live nematodes and their body length, but MWCNT did not affect the population of nematodes. Gene expression analysis revealed significant changes caused by the presence of all studied nanomaterials, and the results strongly suggest a specific metabolic response of the nematode organism to exposure to various nanomaterials. It was shown that C. elegans is a very sensitive organism capable to respond specifically to the exposure to some nanomaterials and therefore could be considered as a possible biosensor for early warning of presence of some nanoparticles.

The aggregation behavior of the amyloid peptide Aβ1-28 and the prion peptide PrP185-208 - 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 PrP185-208 than onto Aβ1-28, while PPI(G5)-Maltotriose is less effective towards PrP185-208 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.