Carbon Quantum Dots for Treatment of Amyloid Disorders

Prion-like amyloids self-template and form toxic oligomers, protofibrils, and fibrils from their soluble monomers; a phenomenon that has been implicated in the onset and progress of neurodegenerative disorders such as Alzheimer's (AD), Parkinson's (PD), Huntington's, and systemic lysozyme amyloidosis. Carbon quantum dots (CQDs), sourced from Na-citrate as a carbon precursor were synthesized and characterized before being tested for their ability to intervene in amyloidogenic (fibril-forming) trajectories. Hen-egg white lysozyme (HEWL) served as a model amyloidogenic protein. A pulse-chase lysozyme fibril-forming assay developed to examine the impact of CQDs on the HEWL amyloid-fibril-forming trajectory used ThT fluorescence as a reporter of mature fibril presence. The results revealed that the Na-citrate-derived CQDs were able to intervene at multiple points along the fibril-forming trajectory by preventing the conversion of both monomeric and oligomeric HEWL intermediates into mature fibrils. In addition, and importantly, the carbon nano material (CNM) was able to dissolve oligomeric HEWL into monomeric HEWL and provoke the disaggregation of mature HEWL fibrils. These results suggest that Na-citrate CQD's intervene in amyloidogenesis by multiple mechanisms. The gathered data, coupled with cell-line results demonstrating the relatively low cytotoxicity of Na-citrate CQDs, suggest that this emerging CNM has the potential to intervene both prophylactically and therapeutically in protein misfolding diseases. The aforementioned findings are likely to enable Na-citrate CQDs to eventually transition to both cell-line and preclinical models of protein-misfolding-related disorders. Importantly, the study outcomes positions Na-citrate CQDs as an important class of chemical, nanotechnological, and biobased interventional tools in neuroscience.

Automated summary

The study found that carbon quantum dots derived from Na-citrate can intervene in the formation of amyloid fibrils, inhibiting the conversion of monomeric and oligomeric intermediates into mature fibrils, and triggering the disaggregation of mature fibrils. These results suggest that the carbon quantum dots have the potential to play a role in both preventing and treating protein misfolding diseases.