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

Abstract

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.