Shaker, M.E., Al-Sanea, M.M., Gomaa, H.A., Imam, M.S., Alosaimi, R.S., Alzahrani, G.A., Alobaywi, K.L.F., Almalawi, J.F., Khojah, H., Shari, F.H., Sayed, A.M. (2025). Targeting amyloid β42 aggregation using a structurally defined graphene quantum dot model: A combined molecular and biological investigation.  Int. J. Biol. Macromol. 321(1): 146205.

FBrf0263174

Research paper

Amyloid beta (Aβ42) aggregation plays a key role in the progression of Alzheimer's disease (AD), contributing to neuronal damage and cognitive impairment. This research examines ovalene, a structurally defined model of graphene quantum dots (GQDs), for its potential to inhibit Aβ42 aggregation. Molecular dynamics simulations indicate that ovalene interferes with Aβ42 protofibril stability in a concentration-dependent manner by disrupting key hydrophobic and aromatic interactions, thus hindering β-sheet formation and fibril growth. Additionally, ovalene prevented Aβ42 dimerization, an early step in amyloid aggregation. Experimental assays, including Thioflavin T fluorescence and circular dichroism, confirmed that ovalene reduces fibril formation while maintaining Aβ42 in its monomeric state. Cytotoxicity studies demonstrated that ovalene counteracts Aβ42-induced toxicity in Neuro-2a cells, with no harmful effects on normal or cancerous cells. In a Drosophila AD model, ovalene significantly lowered amyloid levels, showing the strongest effect at 2 mg/mL. These results support GQD's potential as an anti-amyloid therapy.