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

Abstract 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 ad...

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Autores principales:	Sagnik Sen, Ashmita Dey, Ujjwal Maulik
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ca44653ca77f4ff5a48af0756641bcf0
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spelling	oai:doaj.org-article:ca44653ca77f4ff5a48af0756641bcf02021-12-02T19:06:40ZStudying the effect of alpha-synuclein and Parkinson’s disease linked mutants on inter pathway connectivities10.1038/s41598-021-95889-52045-2322https://doaj.org/article/ca44653ca77f4ff5a48af0756641bcf02021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95889-5https://doaj.org/toc/2045-2322Abstract 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.Sagnik SenAshmita DeyUjjwal MaulikNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sagnik Sen Ashmita Dey Ujjwal Maulik Studying the effect of alpha-synuclein and Parkinson’s disease linked mutants on inter pathway connectivities
description	Abstract 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	article
author	Sagnik Sen Ashmita Dey Ujjwal Maulik
author_facet	Sagnik Sen Ashmita Dey Ujjwal Maulik
author_sort	Sagnik Sen
title	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_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_sort	studying the effect of alpha-synuclein and parkinson’s disease linked mutants on inter pathway connectivities
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ca44653ca77f4ff5a48af0756641bcf0
work_keys_str_mv	AT sagniksen studyingtheeffectofalphasynucleinandparkinsonsdiseaselinkedmutantsoninterpathwayconnectivities AT ashmitadey studyingtheeffectofalphasynucleinandparkinsonsdiseaselinkedmutantsoninterpathwayconnectivities AT ujjwalmaulik studyingtheeffectofalphasynucleinandparkinsonsdiseaselinkedmutantsoninterpathwayconnectivities
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Studying the effect of alpha-synuclein and Parkinson’s disease linked mutants on inter pathway connectivities

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