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Potent prion-like behaviors of pathogenic α-synuclein and evaluation of inactivation methods

The concept that abnormal protein aggregates show prion-like propagation between cells has been considered to explain the onset and progression of many neurodegenerative diseases. Indeed, both synthetic amyloid-like fibrils and pathogenic proteins extracted from patients’ brains induce self-template...

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Autores principales: Tarutani, Airi, Arai, Tetsuaki, Murayama, Shigeo, Hisanaga, Shin-ichi, Hasegawa, Masato
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907316/
https://www.ncbi.nlm.nih.gov/pubmed/29669601
http://dx.doi.org/10.1186/s40478-018-0532-2
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author Tarutani, Airi
Arai, Tetsuaki
Murayama, Shigeo
Hisanaga, Shin-ichi
Hasegawa, Masato
author_facet Tarutani, Airi
Arai, Tetsuaki
Murayama, Shigeo
Hisanaga, Shin-ichi
Hasegawa, Masato
author_sort Tarutani, Airi
collection PubMed
description The concept that abnormal protein aggregates show prion-like propagation between cells has been considered to explain the onset and progression of many neurodegenerative diseases. Indeed, both synthetic amyloid-like fibrils and pathogenic proteins extracted from patients’ brains induce self-templated amplification and cell-to-cell transmission in vitro and in vivo. However, it is unclear whether exposure to exogenous prion-like proteins can potentially cause these diseases in humans. Here, we investigated in detail the prion-like seeding activities of several kinds of pathogenic α-synuclein (α-syn), including synthetic fibrils and detergent-insoluble fractions extracted from brains of patients with α-synucleinopathies. Exposure to synthetic α-syn fibrils at concentrations above 100 pg/mL caused seeded aggregation of α-syn in SH-SY5Y cells, and seeded aggregation was also observed in C57BL/6 J mice after intracerebral inoculation of at least 0.1 μg/animal. α-Syn aggregates extracted from brains of multiple system atrophy (MSA) patients showed higher seeding activity than those extracted from patients with dementia with Lewy bodies (DLB), and their potency was similar to that of synthetic α-syn fibrils. We also examined the effects of various methods that have been reported to inactivate abnormal prion proteins (PrP(Sc)), including autoclaving at various temperatures, exposure to sodium dodecyl sulfate (SDS), and combined treatments. The combination of autoclaving and 1% SDS substantially reduced the seeding activities of synthetic α-syn fibrils and α-syn aggregates extracted from MSA brains. However, single treatment with 1% SDS or generally used sterilization conditions proved insufficient to prevent accumulation of pathological α-syn. In conclusion, α-syn aggregates derived from MSA patients showed a potent prion-like seeding activity, which could be efficiently reduced by combined use of SDS and autoclaving. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-018-0532-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-59073162018-04-30 Potent prion-like behaviors of pathogenic α-synuclein and evaluation of inactivation methods Tarutani, Airi Arai, Tetsuaki Murayama, Shigeo Hisanaga, Shin-ichi Hasegawa, Masato Acta Neuropathol Commun Research The concept that abnormal protein aggregates show prion-like propagation between cells has been considered to explain the onset and progression of many neurodegenerative diseases. Indeed, both synthetic amyloid-like fibrils and pathogenic proteins extracted from patients’ brains induce self-templated amplification and cell-to-cell transmission in vitro and in vivo. However, it is unclear whether exposure to exogenous prion-like proteins can potentially cause these diseases in humans. Here, we investigated in detail the prion-like seeding activities of several kinds of pathogenic α-synuclein (α-syn), including synthetic fibrils and detergent-insoluble fractions extracted from brains of patients with α-synucleinopathies. Exposure to synthetic α-syn fibrils at concentrations above 100 pg/mL caused seeded aggregation of α-syn in SH-SY5Y cells, and seeded aggregation was also observed in C57BL/6 J mice after intracerebral inoculation of at least 0.1 μg/animal. α-Syn aggregates extracted from brains of multiple system atrophy (MSA) patients showed higher seeding activity than those extracted from patients with dementia with Lewy bodies (DLB), and their potency was similar to that of synthetic α-syn fibrils. We also examined the effects of various methods that have been reported to inactivate abnormal prion proteins (PrP(Sc)), including autoclaving at various temperatures, exposure to sodium dodecyl sulfate (SDS), and combined treatments. The combination of autoclaving and 1% SDS substantially reduced the seeding activities of synthetic α-syn fibrils and α-syn aggregates extracted from MSA brains. However, single treatment with 1% SDS or generally used sterilization conditions proved insufficient to prevent accumulation of pathological α-syn. In conclusion, α-syn aggregates derived from MSA patients showed a potent prion-like seeding activity, which could be efficiently reduced by combined use of SDS and autoclaving. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-018-0532-2) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-18 /pmc/articles/PMC5907316/ /pubmed/29669601 http://dx.doi.org/10.1186/s40478-018-0532-2 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Tarutani, Airi
Arai, Tetsuaki
Murayama, Shigeo
Hisanaga, Shin-ichi
Hasegawa, Masato
Potent prion-like behaviors of pathogenic α-synuclein and evaluation of inactivation methods
title Potent prion-like behaviors of pathogenic α-synuclein and evaluation of inactivation methods
title_full Potent prion-like behaviors of pathogenic α-synuclein and evaluation of inactivation methods
title_fullStr Potent prion-like behaviors of pathogenic α-synuclein and evaluation of inactivation methods
title_full_unstemmed Potent prion-like behaviors of pathogenic α-synuclein and evaluation of inactivation methods
title_short Potent prion-like behaviors of pathogenic α-synuclein and evaluation of inactivation methods
title_sort potent prion-like behaviors of pathogenic α-synuclein and evaluation of inactivation methods
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907316/
https://www.ncbi.nlm.nih.gov/pubmed/29669601
http://dx.doi.org/10.1186/s40478-018-0532-2
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