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Studying the effect of alpha-synuclein and Parkinson’s disease linked mutants on inter pathway connectivities
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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358055/ https://www.ncbi.nlm.nih.gov/pubmed/34381149 http://dx.doi.org/10.1038/s41598-021-95889-5 |
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author | Sen, Sagnik Dey, Ashmita Maulik, Ujjwal |
author_facet | Sen, Sagnik Dey, Ashmita Maulik, Ujjwal |
author_sort | Sen, Sagnik |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8358055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-83580552021-08-13 Studying the effect of alpha-synuclein and Parkinson’s disease linked mutants on inter pathway connectivities Sen, Sagnik Dey, Ashmita Maulik, Ujjwal Sci Rep Article 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. Nature Publishing Group UK 2021-08-11 /pmc/articles/PMC8358055/ /pubmed/34381149 http://dx.doi.org/10.1038/s41598-021-95889-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sen, Sagnik Dey, Ashmita Maulik, Ujjwal Studying the effect of alpha-synuclein and Parkinson’s disease linked mutants on inter pathway connectivities |
title | Studying the effect of alpha-synuclein and Parkinson’s disease linked mutants on inter pathway connectivities |
title_full | Studying the effect of alpha-synuclein and Parkinson’s disease linked mutants on inter pathway connectivities |
title_fullStr | Studying the effect of alpha-synuclein and Parkinson’s disease linked mutants on inter pathway connectivities |
title_full_unstemmed | Studying the effect of alpha-synuclein and Parkinson’s disease linked mutants on inter pathway connectivities |
title_short | Studying the effect of alpha-synuclein and Parkinson’s disease linked mutants on inter pathway connectivities |
title_sort | studying the effect of alpha-synuclein and parkinson’s disease linked mutants on inter pathway connectivities |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358055/ https://www.ncbi.nlm.nih.gov/pubmed/34381149 http://dx.doi.org/10.1038/s41598-021-95889-5 |
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