In silico analysis of deleterious p53 SNPs in Parkinson’s Disease

Tumor suppressor p53 is a transcription factor associated with apoptosis or programmed cell death as it is responsible for activating several caspases and downstream apoptotic signaling cascades which leads to cell death. Apoptosis is crucial for maintaining different cellular and biological processes within the organism like genome stability and integrity and cell cycle regulation. Apoptosis plays a major role in progression of neurodegenerative diseases (NDDs) like Parkinson’s disease (PD) where substantial loss of neuronal cells which secrete Dopamine takes place mediated by upregulated expression of p53 protein. In this study we have targeted the missense single nucleotide polymorphs (msSNPs) of p53 which are not reported to be significantly associated with any disease using in silico analysis tools. Structural stability and evolutionary studies have identified eight SNPs to be the most conserved which were further used in this study. All eight variants were found to be most deleterious in accordance with their docking score with MDM2 (inhibitor of p53), which theoretically suggests that apoptosis in cells with these p53 mutations may be less due to high binding affinity of the variants towards MDM2 and thus provide a new insight about potential therapeutic strategies for treating NDDs like PD.