Targeting amyloid β₄₂ aggregation using a structurally defined graphene quantum dot model: A combined molecular and...

Area of Science:

• Biochemistry
• Neuroscience
• Materials Science

Background:

• Amyloid beta (Aβ42) aggregation is central to Alzheimer's disease (AD) pathogenesis, causing neuronal dysfunction and cognitive decline.
• Developing effective inhibitors of Aβ42 aggregation is crucial for AD therapeutic strategies.

Purpose of the Study:

• To investigate ovalene, a graphene quantum dot (GQD) model, as a potential inhibitor of Aβ42 aggregation.
• To evaluate ovalene's efficacy in preventing Aβ42-induced neurotoxicity and its effects in an AD model.

Main Methods:

• Molecular dynamics simulations to assess ovalene's interaction with Aβ42.
• Biochemical assays including Thioflavin T fluorescence and circular dichroism to monitor Aβ42 aggregation.
• In vitro cytotoxicity assays using Neuro-2a cells and an in vivo Drosophila AD model.

Main Results:

• Ovalene disrupted Aβ42 protofibril stability by interfering with hydrophobic and aromatic interactions, hindering β-sheet formation.
• Ovalene prevented Aβ42 dimerization and reduced fibril formation, maintaining Aβ42 in its monomeric state.
• Ovalene mitigated Aβ42-induced cytotoxicity in cells and significantly reduced amyloid levels in a Drosophila AD model.

Conclusions:

• Ovalene demonstrates significant potential to inhibit Aβ42 aggregation and counteract associated toxicity.
• Graphene quantum dots, exemplified by ovalene, show promise as a novel therapeutic approach for Alzheimer's disease.