Athiyah Layla, Sri Widyarti, Sutiman Bambang Sumitro
Context: Parkinson´s disease (PD) is caused by protein aggregates composed of α-synuclein (αSyn) and its pathologies, such as mitochondrial dysfunction, loss of dopamine neurons, dysregulation of the dopamine transporter (DAT), and absorption of αSyn. Treatment with L-DOPA could not overcome it. Therefore, it requires complementary therapy with H2O2 low dose. Aims: To evaluate the potential of H2O2 as a complementary therapy with L-DOPA. Methods: The three-dimensional (3D) ligand and protein target structures were retrieved from PubChem and Protein Data Bank (PDB). H2O2, as ligand, was converted using the Open Babel, which integrated with PyRx v.0.9.8. The molecular docking program used AutoDock Vina as a plug-in in PyRx v.0.9.8. Docking visualization results were analyzed using PyMOL v.2.5.5 (Schrodinger, LLC) and Discovery Studio 2021 Client v21.1.0.20298. The protein-protein docking program used an HDOCK server (Lab of Biophysics and Molecular Modeling, Huazhong University). Molecular dynamics simulation used YASARA Structure v.23.9.29. Results: H2O2 could prevent the formation of αSyn fibrils by reducing the binding affinity between αSyn proteins. H2O2 could avoid mitochondrial dysfunction and loss of dopamine neurons by preventing αSyn binding to VDAC. Dysregulation of the DAT could be avoided by the ability of H2O2 to prevent αSyn binding DAT and avoid αSyn uptake by preventing αSyn binding to LRP1. Conclusions: The H2O2 low dose has the potential to be a complementary therapy with L-DOPA. © 2025 Journal of Pharmacy & Pharmacognosy Research
Magister Program, Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia; Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia; Indonesia Molecule Institute, Elpico Mall No 23, 2nd floor, Malang, Indonesia
