- For an introduction to Parkinson’s Disease (PD) and the role of metals, see “Atox1-Cu-𝛼Syn Complex Providing Answers about Possible Mechanisms of Aggregation of Lewy Bodies in Parkinson’s Disease”
Researchers at Huazhong University of Science and Technology wanted to see if treating C. Elegans with chelating agents would decrease the overproduction and aggregation of 𝛼Syn. Knowing that 𝛼 synuclein proteins aggregate into Lewy bodies like prion diseases (ie. one misfolded protein causes a cascade that leads to the aggregation of protein clumps), they wanted to know if they could stop this process from occurring, with a goal of identifying possible therapeutics. This group used a FRET (fluorescence resonance energy transfer assay), which can show intracellular aggregation and an amyloid formation, and thioflavin-T (ThT) fluorescence assay, where the used seeds of 𝛼Syn in the presence or absence of copper and iron to see if fibrils would form. They found that copper and iron ions increase the rate that Lewy bodies formed, which could indicate that having lower levels of metals could decrease the rate at which Parkinson’s progresses. They wanted to confirm this result in neuronal cells, though to make sure that the C. Elegans data mirrored data in human cells. They used SH-SY5Y cells and found that the aggregation speed associated with ions could be eliminated by using HSPGs, including heparin, which is already approved to treat various heart conditions involved in blood clotting. They measured these intracellular interactions by looking at the proximity of various involved atoms by measuring spin. Overall, this data gives hope that a therapeutic could be available relatively soon because drugs that already are proven safe and effective for other conditions are more likely to move faster through the approval process for other uses.
Read the paper here:
Li, Y., Yang, C., Wang, S., Yang, D., Zhang, Y., Xu, L., Ma, L., Zheng, J., Petersen, R. B., Zheng, L., Chen, H., & Huang, K. (2020). Copper and iron ions accelerate the prion-like propagation of α-synuclein: A vicious cycle in Parkinson’s disease. International Journal of Biological Macromolecules, 163, 562-573. https://doi.org/10.1016/j.ijbiomac.2020.06.274