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RT-QuIC-based detection of alpha-synuclein seeding activity in brains of dementia with Lewy Body patients and of a transgenic mouse model of synucleinopathy

RT-QuIC is a shaking-based cyclic amplification technique originally developed in the prion field to detect minute amounts of scrapie prion protein (PrP(Sc)). In this study, we applied the RT-QuIC assay to investigate a-synuclein (a-syn) seeding activity in brains of Dementia with Lewy Body (DLB) pa...

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Detalles Bibliográficos
Autores principales: Han, Jung-Youn, Jang, Hyung-Sup, Green, Alison J. E., Choi, Young Pyo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039666/
https://www.ncbi.nlm.nih.gov/pubmed/32041499
http://dx.doi.org/10.1080/19336896.2020.1724608
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author Han, Jung-Youn
Jang, Hyung-Sup
Green, Alison J. E.
Choi, Young Pyo
author_facet Han, Jung-Youn
Jang, Hyung-Sup
Green, Alison J. E.
Choi, Young Pyo
author_sort Han, Jung-Youn
collection PubMed
description RT-QuIC is a shaking-based cyclic amplification technique originally developed in the prion field to detect minute amounts of scrapie prion protein (PrP(Sc)). In this study, we applied the RT-QuIC assay to investigate a-synuclein (a-syn) seeding activity in brains of Dementia with Lewy Body (DLB) patients and in brains of G2-3 transgenic mice expressing human a-syn with A53T mutation. The results show that a-syn seeding activity varies between patients with detectable dilutions ranging from 10(−3) to 10(−8) dilutions of brain tissue and is stable under exposures to the cycles of freezing, thawing and sonication. A53T a-syn aggregates from G2-3 transgenic mice greatly favoured A53T recombinant human a-syn as substrates in comparison to wild-type a-syn, suggesting that conformations for wild-type a-syn to be able to adopt are not compatible with that of A53T aggregates from G2-3.
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spelling pubmed-70396662020-03-03 RT-QuIC-based detection of alpha-synuclein seeding activity in brains of dementia with Lewy Body patients and of a transgenic mouse model of synucleinopathy Han, Jung-Youn Jang, Hyung-Sup Green, Alison J. E. Choi, Young Pyo Prion Short Communication RT-QuIC is a shaking-based cyclic amplification technique originally developed in the prion field to detect minute amounts of scrapie prion protein (PrP(Sc)). In this study, we applied the RT-QuIC assay to investigate a-synuclein (a-syn) seeding activity in brains of Dementia with Lewy Body (DLB) patients and in brains of G2-3 transgenic mice expressing human a-syn with A53T mutation. The results show that a-syn seeding activity varies between patients with detectable dilutions ranging from 10(−3) to 10(−8) dilutions of brain tissue and is stable under exposures to the cycles of freezing, thawing and sonication. A53T a-syn aggregates from G2-3 transgenic mice greatly favoured A53T recombinant human a-syn as substrates in comparison to wild-type a-syn, suggesting that conformations for wild-type a-syn to be able to adopt are not compatible with that of A53T aggregates from G2-3. Taylor & Francis 2020-02-10 /pmc/articles/PMC7039666/ /pubmed/32041499 http://dx.doi.org/10.1080/19336896.2020.1724608 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communication
Han, Jung-Youn
Jang, Hyung-Sup
Green, Alison J. E.
Choi, Young Pyo
RT-QuIC-based detection of alpha-synuclein seeding activity in brains of dementia with Lewy Body patients and of a transgenic mouse model of synucleinopathy
title RT-QuIC-based detection of alpha-synuclein seeding activity in brains of dementia with Lewy Body patients and of a transgenic mouse model of synucleinopathy
title_full RT-QuIC-based detection of alpha-synuclein seeding activity in brains of dementia with Lewy Body patients and of a transgenic mouse model of synucleinopathy
title_fullStr RT-QuIC-based detection of alpha-synuclein seeding activity in brains of dementia with Lewy Body patients and of a transgenic mouse model of synucleinopathy
title_full_unstemmed RT-QuIC-based detection of alpha-synuclein seeding activity in brains of dementia with Lewy Body patients and of a transgenic mouse model of synucleinopathy
title_short RT-QuIC-based detection of alpha-synuclein seeding activity in brains of dementia with Lewy Body patients and of a transgenic mouse model of synucleinopathy
title_sort rt-quic-based detection of alpha-synuclein seeding activity in brains of dementia with lewy body patients and of a transgenic mouse model of synucleinopathy
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039666/
https://www.ncbi.nlm.nih.gov/pubmed/32041499
http://dx.doi.org/10.1080/19336896.2020.1724608
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