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Quiescent Elongation of α-Synuclein Pre-form Fibrils Under Different Solution Conditions

The intracellular aggregation of α-synuclein in neurons/glia is considered to be a key step in the pathogenesis of synucleinopathy [including Parkinson’s disease (PD), dementia with Lewy body (DLB), multiple system atrophy (MSA), etc.]. Increasing evidence indicates that the initial pathological α-s...

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Autores principales: Mao, Hengxu, Ye, Yongyi, Sun, Xiang, Qian, Chen, Wang, Baoyan, Xie, Linghai, Zhang, Shizhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175570/
https://www.ncbi.nlm.nih.gov/pubmed/35692426
http://dx.doi.org/10.3389/fnins.2022.902077
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author Mao, Hengxu
Ye, Yongyi
Sun, Xiang
Qian, Chen
Wang, Baoyan
Xie, Linghai
Zhang, Shizhong
author_facet Mao, Hengxu
Ye, Yongyi
Sun, Xiang
Qian, Chen
Wang, Baoyan
Xie, Linghai
Zhang, Shizhong
author_sort Mao, Hengxu
collection PubMed
description The intracellular aggregation of α-synuclein in neurons/glia is considered to be a key step in the pathogenesis of synucleinopathy [including Parkinson’s disease (PD), dementia with Lewy body (DLB), multiple system atrophy (MSA), etc.]. Increasing evidence indicates that the initial pathological α-synuclein aggregates can replicate themselves and propagate in a “seeding” manner to multiple areas of the brain and even to peripheral tissue, which makes it the most important biomarker for the diagnosis of synucleinopathies in recent years. The amplification and propagation capabilities of α-synuclein aggregates are very similar to those of prion-like diseases, which are based on the inherent self-recruitment capabilities of existing misfolded proteins. In vitro, the rapid recruitment process can be reproduced in a simplified model by adding a small amount of α-synuclein pre-formed fibrils to the monomer solution as fibril seeds, which may partially reveal the properties of α-synuclein aggregates. In this study, we explored the elongation rate of α-synuclein pre-formed fibrils under a quiescent incubation condition (rather than shaking/agitating). By using the ThT fluorescence assay, we compared and quantified the elongation fluorescence curves to explore the factors that affect fibril elongation. These factors include proteins’ concentration, temperature, NaCl strength, SDS, temperature pretreatment, and so on. Our work further describes the elongation of α-synuclein fibrils under quiescent incubation conditions. This may have important implications for the in vitro amplification and preservation of α-synuclein aggregates to further understand the prion-like transmission mechanism of PD.
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spelling pubmed-91755702022-06-09 Quiescent Elongation of α-Synuclein Pre-form Fibrils Under Different Solution Conditions Mao, Hengxu Ye, Yongyi Sun, Xiang Qian, Chen Wang, Baoyan Xie, Linghai Zhang, Shizhong Front Neurosci Neuroscience The intracellular aggregation of α-synuclein in neurons/glia is considered to be a key step in the pathogenesis of synucleinopathy [including Parkinson’s disease (PD), dementia with Lewy body (DLB), multiple system atrophy (MSA), etc.]. Increasing evidence indicates that the initial pathological α-synuclein aggregates can replicate themselves and propagate in a “seeding” manner to multiple areas of the brain and even to peripheral tissue, which makes it the most important biomarker for the diagnosis of synucleinopathies in recent years. The amplification and propagation capabilities of α-synuclein aggregates are very similar to those of prion-like diseases, which are based on the inherent self-recruitment capabilities of existing misfolded proteins. In vitro, the rapid recruitment process can be reproduced in a simplified model by adding a small amount of α-synuclein pre-formed fibrils to the monomer solution as fibril seeds, which may partially reveal the properties of α-synuclein aggregates. In this study, we explored the elongation rate of α-synuclein pre-formed fibrils under a quiescent incubation condition (rather than shaking/agitating). By using the ThT fluorescence assay, we compared and quantified the elongation fluorescence curves to explore the factors that affect fibril elongation. These factors include proteins’ concentration, temperature, NaCl strength, SDS, temperature pretreatment, and so on. Our work further describes the elongation of α-synuclein fibrils under quiescent incubation conditions. This may have important implications for the in vitro amplification and preservation of α-synuclein aggregates to further understand the prion-like transmission mechanism of PD. Frontiers Media S.A. 2022-05-25 /pmc/articles/PMC9175570/ /pubmed/35692426 http://dx.doi.org/10.3389/fnins.2022.902077 Text en Copyright © 2022 Mao, Ye, Sun, Qian, Wang, Xie and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Mao, Hengxu
Ye, Yongyi
Sun, Xiang
Qian, Chen
Wang, Baoyan
Xie, Linghai
Zhang, Shizhong
Quiescent Elongation of α-Synuclein Pre-form Fibrils Under Different Solution Conditions
title Quiescent Elongation of α-Synuclein Pre-form Fibrils Under Different Solution Conditions
title_full Quiescent Elongation of α-Synuclein Pre-form Fibrils Under Different Solution Conditions
title_fullStr Quiescent Elongation of α-Synuclein Pre-form Fibrils Under Different Solution Conditions
title_full_unstemmed Quiescent Elongation of α-Synuclein Pre-form Fibrils Under Different Solution Conditions
title_short Quiescent Elongation of α-Synuclein Pre-form Fibrils Under Different Solution Conditions
title_sort quiescent elongation of α-synuclein pre-form fibrils under different solution conditions
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175570/
https://www.ncbi.nlm.nih.gov/pubmed/35692426
http://dx.doi.org/10.3389/fnins.2022.902077
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