An Assessment of the Role of Redox Metals Causing Oxidative Stress in Parkinson's Disease

Redox metal ions are involved in the pathogenesis of Parkinson's disease(PD), and researchers have been studying and developing novel therapeutic chelating agents for the treatment. Chelation therapy is an effective form of treatment for neurodegenerative diseases, and the proper molecule is needed to perform this task of reducing metal ion levels that can be harmful by producing reactive oxygen species(ROS) and damaging cells in the brain. Through computational analysis of various confirmed metal ion chelators, certain compounds such as metal-organic frameworks(MOFs) molecules and chelators were modeled and analyzed to figure out their efficiencies as chelators for the therapy of PD. Among the tested molecules, for example, UiO-66-BDC showed thermodynamically stable and extremely high reactivity. Additionally, its high surface area to volume ratio allows it to have a significantly higher uptake of redox-active metals relative to other chelators.

Our findings can be indicative of the potential role of metal metabolism and PD pathogenesis. Further modeling of other metal ion chelators such as EDTA was conducted to explore more candidates further. To determine the theoretical values of a certain structure’s atomic properties, such as enthalpy, bond strength, and electron distributions, the Density Functional Theory (DFT) was used. The software used in this paper allows users to build virtually any molecule and optimize its geometry according to various force field options.