School of Medicine Publications and Presentations
Document Type
Article
Publication Date
6-2025
Abstract
Background: α-synuclein (α-syn) deposition in the mid-brain region is one of the hallmark pathologies of Parkinson's disease (PD). The key steps involve the transformation of α-synuclein into a toxic oligomer and insoluble fibrillar aggregates.
Objective: To understand the role of curcumin-glucoside in the prevention of α-syn aggregation, a mechanistic approach.
Methods: In the present study, we synthesized a novel molecule, curcumin-glucoside (Curc-gluc), to improve the water solubility and partition coefficient, making the molecule with high bioavailability. The present study is focused on understanding the α-syn aggregation kinetics in the presence and absence of Curc-gluc, curcumin (Cur), copper (Cu), and iron (Fe) through Thioflavin T analysis, circular dichroism (CD), mathematical approach by self-association kinetics, and molecular docking models.
Results: The results indicated that Curc-gluc potentially prevented synuclein aggregation compared to Curc alone and inhibited Cu and Fe-induced synuclein aggregation. CD studies indicated that Curc-gluc favored α-helix formation. The docking studies indicated that Curc-gluc derivatives interacted with various chains of α-syn fibrils, namely G-chain, A-chain, I-Chain, and E-chain and the Pi-Pi interaction indicate that, Curc-gluc shows the most favorable binding affinity with the α-syn fibrils with 60.7222 kcal/mol of -CDOCKER_ ENERGY and 89.6516 kcal/mol of -CDOCKER INTERACTION_ ENERGY. The Absorption, Distribution, Metabolism, Excretion (ADME) analysis indicated that Curc-mono and di-gluc have the highest solubility, bioavailability, and tissue distribution compared to Curc alone.
Conclusions: The studies indicated that Curc-gluc prevented α-syn aggregation by favoring α-helix, binding to α-syn, and preventing aggregation, and had high bioavailability.
Recommended Citation
Emani, L. S., Rao, J. K., Kumar Dasappa, J., Pecchio, M., Lakey-Beitia, J., Rodriguez, H., Cruz-Mora, J., Narayan, P., Anand, N., Mullur, G., Ajumeera, R., Gadad, B. S., & Kosagisharaf, J. R. (2025). Studies on curcumin-glucoside in the prevention of alpha-synuclein aggregation. Journal of Alzheimer's disease reports, 9, 25424823251347260. https://doi.org/10.1177/25424823251347260
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Publication Title
Journal of Alzheimer's disease reports
DOI
10.1177/25424823251347260
Academic Level
faculty
Mentor/PI Department
Medical Education
Comments
© The Author(s) 2025
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