The Molecular Mechanism of Vitamin D3 in Mitigating Pathological Formation of Parkinson’s Disease


  • Brianna Kwan Poly Prep Country Day School
  • Dr. Wei Zhu 1Poly Prep Country Day School



Vitamin D3, Parkinson's Disease, mitochondrial complex I, PD, Rotenone


Parkinson’s Disease (PD) has been in the spotlight of research for decades, but despite efforts aiming to discover treatments, there is still no effective therapy that targets PD pathology. Vitamin D3, however, has been identified as a promising chemical in mitigating the effects of alpha synuclein (⍺-syn), a hallmark protein in diagnosing PD. Mitochondrial complex I is a protein complex that produces oxidative stress, an effect that can lead to symptoms of PD. Rotenone, a chemical which induces PD-like effects was used to set a PD model. This study focused on the anti-PD effects of vitamin D3 in attenuating rotenone through mitochondrial complex I. Treatments were tested by measuring cell proliferation, rotenone induced necrosis, and rotenone induced apoptosis. Varying concentrations of vitamin D3 proved to reduce cytotoxicity substantially. Caspase activity in apoptosis decreased with vitamin D3 presence, suggesting that cell death was mitigated. In addition to using in vitro rotenone PD models, molecular docking was used to depict vitamin D3, rotenone, and mitochondrial complex I interactions. To our knowledge, this was the first study to use vitamin D3 and mitochondrial complex I in a molecular docking analysis in addition to utilizing rotenone to study PD. Docking established a connection between mitochondrial complex I, rotenone, and vitamin D3 by displaying a strong bond between molecules. This ultimately suggested that vitamin D3 can indirectly mitigate oxidative stress by attenuating rotenone and ⍺-syn through mitochondrial complex I, thus limiting the presence of ⍺-syn, which is seen in elevated amounts in PD. 


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Author Biography

Dr. Wei Zhu, 1Poly Prep Country Day School


References or Bibliography

Askew, F. A., Bourdillon, R. B., Bruce, H. M., Jenkins, R. G. C., & Webster, T. A. (1930, September 3). The distillation of vitamin D. Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character.

Betarbet , R., Sherer, T. B., MacKenzie, G., Garcia-Osuna, M., Panov, A. V., & Greenamyre, J. T. (2000, December). Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nature neuroscience.

Deluca, H. F. (2014, January 8). History of the discovery of vitamin D and its active metabolites. BoneKEy reports.

DeMaagd, G., & Philip, A. (2015). Parkinson's Disease and Its Management: Part 1: Disease Entity, Risk Factors, Pathophysiology, Clinical Presentation, and Diagnosis. P & T : a peer-reviewed journal for formulary management, 40(8), 504–532.

Environmental Factors. Parkinson's Foundation. (n.d.).

E. Ray Dorsey, M. D. (2018, January 1). The Parkinson Pandemic. JAMA Neurology. doi:10.1001/jamaneurol.2017.3299

Genetics and Parkinson's. Parkinson's Foundation. (n.d.).

Gómez-Benito, M., Granado, N., García-Sanz, P., Michel, A., Dumoulin, M., & Moratalla, R. (2020). Modeling Parkinson's Disease With the Alpha-Synuclein Protein. Frontiers in pharmacology, 11, 356.

Grünewald, A., Kumar, K. R., & Sue, C. M. (2018, September 13). New insights into the complex role of mitochondria in Parkinson's disease. Progress in Neurobiology.

Jackson-Lewis, V., Blesa, J., & Przedborski, S. (2012, January 1). Animal models of Parkinson's disease. Parkinsonism & Related Disorders.

Jang, W., Kim, H. J., Li, H., Jo, K. D., Lee, M. K., Song, S. H., & Yang, H. O. (2014, July 29). 1,25-Dihydroxyvitamin D₃ attenuates rotenone-induced neurotoxicity in SH-SY5Y cells through induction of autophagy. Biochemical and biophysical research communications.

Lazo, C. R., Guillot, T. S., & Miller, G. W. (2014, May 1). Rotenone. Encyclopedia of the Neurological Sciences (Second Edition).

Li, N., Ragheb, K., Lawler, G., Sturgis, J., Rajwa, B., Melendez, J. A., & Robinson, J. P. (2021, January 4). Mitochondrial Complex I Inhibitor Rotenone Induces Apoptosis through Enhancing Mitochondrial Reactive Oxygen Species Production. Journal of Biological Chemistry.

Liebeschuetz, John. (2015). Re: What is the importance of the RMSD value in molecular docking?. Retrieved from:

Luo, X., Ou, R., Dutta, R., Tian, Y., Xiong, H., & Shang, H. (1AD, January 1). Association Between Serum Vitamin D Levels and Parkinson's Disease: A Systematic Review and Meta-Analysis. Frontiers.

Marella, M., Seo, B. B., Yagi, T., & Matsuno-Yagi, A. (2009, December). Parkinson's disease and mitochondrial complex I: a perspective on the Ndi1 therapy. Journal of bioenergetics and biomembranes.

Nat Struct Mol Biol 9, 77 (2002). A dose of vitamin D history. Nature News.

Perron, G. G., Zasloff, M., & Bell, G. (2006, January 22). Experimental evolution of resistance to an antimicrobial peptide. Proceedings. Biological sciences.

​​Peterson, A. L., Mancini, M., & Horak, F. B. (2013, April 2). The relationship between balance control and vitamin D in Parkinson's disease-a pilot study. International Parkinson and Movement Disorder Society.

Pouchieu C;Piel C;Carles C;Gruber A;Helmer C;Tual S;Marcotullio E;Lebailly P;Baldi I; (n.d.). Pesticide use in agriculture and Parkinson's disease in the AGRICAN cohort study. International journal of epidemiology.

Radad, K., Al-Shraim, M., Al-Emam, A., Wang, F., Kranner, B., Rausch, W.-D., & Moldzio, R. (2019, November 18). Rotenone: from modelling to implication in Parkinson's disease. Folia Neuropathologica.

Rcom-H'cheo-Gauthier, A. N., Meedeniya, A. C. B., & Pountney, D. L. (2017, April 6). Calcipotriol inhibits ⍺‐synuclein aggregation in SH‐SY5Y neuroblastoma cells by a Calbindin‐D28k‐dependent mechanism. Wiley Online Library.

Rimmelzwaan, L. M., van Schoor, N. M., Lips, P., Berendse, H. W., & Eekhoff, E. M. W. (2016, January 1). Systematic Review of the Relationship between Vitamin D and Parkinson's Disease. Journal of Parkinson's Disease.

Statistics. Parkinson's Foundation. (n.d.).

The Genetic Link to Parkinson's Disease. Johns Hopkins Medicine. (n.d.).

U.S. Department of Health and Human Services. (n.d.). Parkinson's Disease Information Page. National Institute of Neurological Disorders and Stroke.



How to Cite

Kwan, B., & Zhu, W. (2022). The Molecular Mechanism of Vitamin D3 in Mitigating Pathological Formation of Parkinson’s Disease. Journal of Student Research, 11(2).



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