Abstract: “Alzheimer’s disease is a neurodegenerative disease currently found in some of our aging population. One key feature of the disease is the observation of deposits of the small peptide Amyloid-Beta (Aβ). The goal of using ruthenium-based (Ru) compounds is to prevent the aggregation of Aβ, thereby decreasing the formation of Aβ plaques. Two Ru compounds were synthesized using quinoline derivatives. The compounds were then studied by a Thioflavin T assay and Dynamic light scattering. Both compounds were also characterized by NMR and ESI-MS spectroscopy and found to be consistent with literature values. Next, the complexes were evaluated for their ability to inhibit the aggregation of the Aβ peptide, with C2 showing a strong inhibition of the peptide. The compounds have been found to inhibit the Aβ aggregation, but there has yet to be a cytotoxicity screening toward glial cells to ensure the compounds are not cytotoxic. Both compounds have promise, but there are more tests necessary to determine their actual benefit.”
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Hi Cade!
Great work! I also just have a few questions:
– Have you done any work to try to definitively elucidate where exactly these compounds would be complexing in the peptide chain?
– How do you envision administering this type of compound? I guess more specifically, how can these types of compounds be given to patients to ensure that they are interacting with plaques in the brain and not other proteins elsewhere in the body?
Thank you! Joe
Hello Cade!
Great talk and presentation!
I have a couple of questions:
Why did you choose Ruthenium as your metal choice for this research? Are there any other metals that might also work, or be worth investigating?
What characteristics of Ruthenium lend it to be a good choice?
We chose to use Ruthenium because it had been used previously and has shown some promise. It tends to have low cytotoxicity in the body, and it is in the same group as iron which is abundant in the body, meaning it has similar characteristics. Its similarity to iron should, in theory, allow it to coordinate to the amyloid-beta peptide similar to how iron is believed to coordinate. There are other metals that are currently in research and may work well like Platinum or Iridium or others, but time and money are not limitless so we chose to use Ruthenium.
Thanks for your reply Cade!
Very clear talk and slides thank you. So in your DLS studies, could that second smaller peak be explained simply by the presence of uncomplexed ligand, instead of degraded protein? Also did you do fluorescence studies without the amyloid, to confirm that the Ru compound is not simply quenching the ThT signal?
It is possible that the second peak is due to the uncomplexed ligand. We will get a better idea of what has happened with the protein once we have TEM images. The fluorescence studies were done without the amyloid as well, and the results you see have been corrected for the fluorescence of the compound without the amyloid-beta.