Studying the effect of alpha-synuclein and Parkinson’s disease linked mutants on inter pathway connectivities

• Published in: Scientific reports Vol. 11; no. 1; p. 16365
• Main Authors: Sen, Sagnik, Dey, Ashmita, Maulik, Ujjwal
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11-08-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114; 631/114/663; alpha-Synuclein - genetics; Comparative studies; Computational neuroscience; Dopamine - genetics; Dopamine receptors; Humanities and Social Sciences; Humans; Lewy bodies; Missense mutation; Mitochondria; Mitochondria - genetics; Mitochondrial Diseases - genetics; Movement disorders; multidisciplinary; Mutants; Mutation; Mutation - genetics; Neural networks; Neurodegenerative diseases; Parkinson Disease - genetics; Parkinson's disease; Protein Aggregation, Pathological - genetics; Proteins; Science; Science (multidisciplinary); Signal Transduction - genetics; Synuclein
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-95889-5

Parkinson’s disease is a common neurodegenerative disease. The differential expression of alpha-synuclein within Lewy Bodies leads to this disease. Some missense mutations of alpha-synuclein may resultant in functional aberrations. In this study, our objective is to verify the functional adaptation due to early and late-onset mutation which can trigger or control the rate of alpha-synuclein aggregation. In this regard, we have proposed a computational model to study the difference and similarities among the Wild type alpha-synuclein and mutants i.e., A30P, A53T, G51D, E46K, and H50Q. Evolutionary sequence space analysis is also performed in this experiment. Subsequently, a comparative study has been performed between structural information and sequence space outcomes. The study shows the structural variability among the selected subtypes. This information assists inter pathway modeling due to mutational aberrations. Based on the structural variability, we have identified the protein–protein interaction partners for each protein that helps to increase the robustness of the inter-pathway connectivity. Finally, few pathways have been identified from 12 semantic networks based on their association with mitochondrial dysfunction and dopaminergic pathways.