Date of Graduation
Fall 2025
Degree
Master of Science in Chemistry
Department
Chemistry & Biochemistry
Committee Chair
Tuhina Banerjee
Abstract
Parkinson’s disease (PD) and other Proteinopathies develop when α-synuclein misfolds and aggregates into toxic amyloids. While existing treatments for PD are primarily focused on managing its symptoms, a viable solution for slowing down the progress of Parkinson’s disease involves targeting the toxic α-synuclein amyloids. Gedunin, a natural inhibitor of heat shock protein 90, has been extensively used to treat malaria. Also, recent research investigations have shed light on its potential beyond malaria therapy, indicating that Gedunin may offer a possible solution for treating a variety of neurodegenerative diseases. Using plate-based assays, we examined how Gedunin influences α-synuclein fibrillation and its impact in the pathophysiology of Parkinson’s. The findings reveal Gedunin dose dependent concentrations modulates the α-syn fibrillation pattern, reducing the buildup of toxic oligomers while increasing their susceptibility to proteolytic breakdown. Gedunin decreases α-synuclein-amyloid toxicity by binding to the hydrophobic parts of α-synuclein oligomers. This suggests that oligomerization may be crucial for α-synuclein to manifest its neurotoxic effects. These results provide convincing proof of Gedunin’s neuroprotective potential in PD by targeting protein misfolding and aggregation, also, they indicate a path forward for treatments that modify the disease course.
Keywords
Parkinson’s disease, α-synuclein, Gedunin, oligomers, toxic amyloids, Plate-based assays, fibrillation
Subject Categories
Amino Acids, Peptides, and Proteins | Medical Biochemistry | Medical Biophysics | Medicinal and Pharmaceutical Chemistry | Medicinal-Pharmaceutical Chemistry | Natural Products Chemistry and Pharmacognosy | Nervous System Diseases | Neurology | Neurosciences | Therapeutics
Copyright
© Tony Matundura Nyabayo
Recommended Citation
Nyabayo, Tony Matundura, "Alpha-Synuclein Interaction With Gedunin" (2025). Graduate Theses/Dissertations. 4124.
https://bearworks.missouristate.edu/theses/4124
Open Access
Included in
Amino Acids, Peptides, and Proteins Commons, Medical Biochemistry Commons, Medical Biophysics Commons, Medicinal and Pharmaceutical Chemistry Commons, Medicinal-Pharmaceutical Chemistry Commons, Natural Products Chemistry and Pharmacognosy Commons, Nervous System Diseases Commons, Neurology Commons, Neurosciences Commons, Therapeutics Commons
