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Effect of Electric Field on α-Synuclein Fibrils: Revealed by Molecular Dynamics Simulations

The self-association of amylogenic proteins to the fibril form is considered a pivotal factor in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). PD causes unintended or uncontrollable movements in its common symptoms. α-synuclein is the major cause of PD developme...

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Autores principales: Razzokov, Jamoliddin, Fazliev, Sunnatullo, Makhkamov, Mukhriddin, Marimuthu, Parthiban, Baev, Artyom, Kurganov, Erkin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10094641/
https://www.ncbi.nlm.nih.gov/pubmed/37047286
http://dx.doi.org/10.3390/ijms24076312
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author Razzokov, Jamoliddin
Fazliev, Sunnatullo
Makhkamov, Mukhriddin
Marimuthu, Parthiban
Baev, Artyom
Kurganov, Erkin
author_facet Razzokov, Jamoliddin
Fazliev, Sunnatullo
Makhkamov, Mukhriddin
Marimuthu, Parthiban
Baev, Artyom
Kurganov, Erkin
author_sort Razzokov, Jamoliddin
collection PubMed
description The self-association of amylogenic proteins to the fibril form is considered a pivotal factor in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). PD causes unintended or uncontrollable movements in its common symptoms. α-synuclein is the major cause of PD development and thus has been the main target of numerous studies to suppress and sequester its expression or effectively degrade it. Nonetheless, to date, there are no efficient and proven ways to prevent pathological protein aggregation. Recent investigations proposed applying an external electric field to interrupt the fibrils. This method is a non-invasive approach that has a certain benefit over others. We performed molecular dynamics (MD) simulations by applying an electric field on highly toxic fibrils of α-synuclein to gain a molecular-level insight into fibril disruption mechanisms. The results revealed that the applied external electric field induces substantial changes in the conformation of the α-synuclein fibrils. Furthermore, we show the threshold value for electric field strength required to completely disrupt the α-synuclein fibrils by opening the hydrophobic core of the fibril. Thus, our findings might serve as a valuable foundation to better understand molecular-level mechanisms of the α-synuclein fibrils disaggregation process under an applied external electric field.
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spelling pubmed-100946412023-04-13 Effect of Electric Field on α-Synuclein Fibrils: Revealed by Molecular Dynamics Simulations Razzokov, Jamoliddin Fazliev, Sunnatullo Makhkamov, Mukhriddin Marimuthu, Parthiban Baev, Artyom Kurganov, Erkin Int J Mol Sci Article The self-association of amylogenic proteins to the fibril form is considered a pivotal factor in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). PD causes unintended or uncontrollable movements in its common symptoms. α-synuclein is the major cause of PD development and thus has been the main target of numerous studies to suppress and sequester its expression or effectively degrade it. Nonetheless, to date, there are no efficient and proven ways to prevent pathological protein aggregation. Recent investigations proposed applying an external electric field to interrupt the fibrils. This method is a non-invasive approach that has a certain benefit over others. We performed molecular dynamics (MD) simulations by applying an electric field on highly toxic fibrils of α-synuclein to gain a molecular-level insight into fibril disruption mechanisms. The results revealed that the applied external electric field induces substantial changes in the conformation of the α-synuclein fibrils. Furthermore, we show the threshold value for electric field strength required to completely disrupt the α-synuclein fibrils by opening the hydrophobic core of the fibril. Thus, our findings might serve as a valuable foundation to better understand molecular-level mechanisms of the α-synuclein fibrils disaggregation process under an applied external electric field. MDPI 2023-03-28 /pmc/articles/PMC10094641/ /pubmed/37047286 http://dx.doi.org/10.3390/ijms24076312 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Razzokov, Jamoliddin
Fazliev, Sunnatullo
Makhkamov, Mukhriddin
Marimuthu, Parthiban
Baev, Artyom
Kurganov, Erkin
Effect of Electric Field on α-Synuclein Fibrils: Revealed by Molecular Dynamics Simulations
title Effect of Electric Field on α-Synuclein Fibrils: Revealed by Molecular Dynamics Simulations
title_full Effect of Electric Field on α-Synuclein Fibrils: Revealed by Molecular Dynamics Simulations
title_fullStr Effect of Electric Field on α-Synuclein Fibrils: Revealed by Molecular Dynamics Simulations
title_full_unstemmed Effect of Electric Field on α-Synuclein Fibrils: Revealed by Molecular Dynamics Simulations
title_short Effect of Electric Field on α-Synuclein Fibrils: Revealed by Molecular Dynamics Simulations
title_sort effect of electric field on α-synuclein fibrils: revealed by molecular dynamics simulations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10094641/
https://www.ncbi.nlm.nih.gov/pubmed/37047286
http://dx.doi.org/10.3390/ijms24076312
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