Genetic Variations in SNCA Gene and their Potential Therapeutic Implications for Parkinson’s Disease

Yaghsha Javed, Muhammad Saleem, Hamna Tariq, Kainat Ramzan, Sadia Javeed and Hafiz Abdul Moeed
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Yaghsha Javed: Department of Molecular Biology, Faculty of Life Sciences, University of Okara, Punjab, Pakistan
Muhammad Saleem: Department of Molecular Biology, Faculty of Life Sciences, University of Okara, Punjab, Pakistan
Hamna Tariq: Department of Molecular Biology, Faculty of Life Sciences, University of Okara, Punjab, Pakistan
Kainat Ramzan: Department of Biochemistry, University of Okara, Punjab, Pakistan
Sadia Javeed: Fatima Memorial College, Lahore, Punjab, Pakistan
Hafiz Abdul Moeed: Faculty of Veterinary Science, University of Agriculture Faisalabad, Punjab, Pakistan

International Journal of Research and Innovation in Social Science, 2024, vol. 8, issue 11, 3368-3384

Abstract: Genetic variations play a crucial role in disease pathogenesis and serve as key biomarkers in SNP analysis. Alpha-synuclein (SNCA), a presynaptic protein involved in neuronal plasticity, is implicated in Parkinson’s disease through its abnormal accumulation in Lewy bodies and mutations in the α-synuclein gene. The nsSNPs are known to account for over 50% of genetic disorders, highlighting their importance in the molecular mechanisms underlying PD. In this study, sequence and structure-based web tools were employed to analyze SNCA mutations and their impact on the target protein. We identified disease-associated nsSNPs and predicted structural changes induced by these mutations. Molecular docking studies on both wild-type and mutant SNCA proteins were conducted using the PyRx algorithm. Our results revealed 20,268 SNPs in the SNCA gene regions, only 17 nsSNPs were found to be deleterious and disease-associated. The SNCA protein structure was modeled using the Swiss Model (2kkw.1.A), and model accuracy was evaluated using the SAVES server. Our analysis identified G36S and P138H missense mutations with significant deleterious effects, as indicated by their high RMSD values. Docking studies further highlighted Benazepril (-5.6), Rutin (-6.8), Hesperidin (-7.1), Cilazepril (-5.7), and Ketoconazole (-5.8) as promising candidates for binding with SNCA protein complexes. This study underscores potential therapeutic candidates and provides a foundation for exploring targeted treatments for PD through validation of the identified compounds and further nsSNP analysis. However, further experimental validation and clinical trials are needed to assess their efficacy and safety in PD treatment.

Date: 2024
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