Integrated in silico and in vitro Experimental Strategies for the Application of Carbon Quantum Dots in Alzheimer's Research

Overview

Alzheimer’s is difficult to treat, particularly due to inability of prospective treatments to cross the impermeable blood-brain-barrier(BBB). Neurodegeneration is exacerbated by Aß-aggregates and tau protein, caused by NMDA/AMPA/GSK3-ß dysfunction. This study evaluated the potential of carbon quantum dots(CQDs), nanomaterials exhibiting BBB-crossing, in Alzheimer’s research, using methylene blue(MB) and ginkgolide-a(GA), carbon-rich, accessible substances, as precursors. Molecular docking between ligands(MB,GA) and macromolecules(AMPA,NMDA,GSK3-ß), indicated strong binding affinities(>-5.0kcal/mol). MTT and caspase-3 assays assessing apoptosis were conducted using HTB-11cells. MB/GA increased cell viability and reduced caspase activity in cells exposed to Aß(p=.001, .0002, respectively). An ELISA assessed levels of eotaxin protein, which exhibits BBB-crossing and exacerbate tau-pathology/neuroinflammation. Aß-exposed CCD-18Co cells displayed reduction of eotaxin by MB/GA(p=.015). Assays displayed MB/GA’s potential to influence Alzheimer’s pathology via interactions found by docking. Finally, CQD’s were hydrothermally synthesized using MB/GA. BR6563,CL2120,CL2122 C. elegans expressing tau and Aß respectively, were exposed to CQD’s to evaluate prevalence of neuroprotective effects. Fluorescence levels of Aß/tau in models decreased after CQD exposure, indicating Aß/tau reduction (p=.039). Overall, methods provide a versatile,affordable,green method of addressing Alzheimer’s pathology through CQD’s. CQD’s significantly reduced Aß/tau expression and apoptosis in models. In-silico molecular docking allows for exploration of numerous interactions, and preliminary in-vitro validation of precursors increases chances of maintaining desired neuroprotective-effects post-synthesis.

Awards (1)

• Fourth Award of $500 $500

Competition history

• ISEF 2024 Biomedical and Health Sciences · Entry BMED016 · Los Angeles, California, United States

Resources

• ISEF abstract page ↗

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