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Role of different recombinant PrP substrates in the diagnostic accuracy of the CSF RT-QuIC assay in Creutzfeldt-Jakob disease
The development of the real-time quaking-induced conversion (RT-QuIC), an in vitro protein misfolding amplification assay, was an innovation in the scientific field of protein misfolding diseases. In prion diseases, these types of assays imitate the pathological conversion of the cellular prion prot...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113290/ https://www.ncbi.nlm.nih.gov/pubmed/36536226 http://dx.doi.org/10.1007/s00441-022-03715-9 |
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author | Da Silva Correia, Susana Margarida Schmitz, Matthias Fischer, Andre Hermann, Peter Zerr, Inga |
author_facet | Da Silva Correia, Susana Margarida Schmitz, Matthias Fischer, Andre Hermann, Peter Zerr, Inga |
author_sort | Da Silva Correia, Susana Margarida |
collection | PubMed |
description | The development of the real-time quaking-induced conversion (RT-QuIC), an in vitro protein misfolding amplification assay, was an innovation in the scientific field of protein misfolding diseases. In prion diseases, these types of assays imitate the pathological conversion of the cellular prion protein (PrP(C)) into a protease-resistant and/or amyloid form of PrP, called PrP resistant (PrP(Res)). The RT-QuIC is an automatic assay system based on real-time measuring of thioflavin-T (Th-T) incorporation into amyloid fibrils using shaking for disaggregation. It has already been applied in diagnostics, drug pre-screening, and to distinguish between different prion strains. The seeded conversion efficiency and the diagnostic accuracy of the RT-QuIC assay strongly depend on the kind of recombinant PrP (rec PrP) substrate. The DNA sequences of different substrates may originate from different species, such as human, bank vole, and hamster, or from a combination of two species, e.g., hamster-sheep chimera. In routine use, either full-length (FL) or truncated substrates are applied which can accelerate the conversion reaction, e.g., to a more sensitive version of RT-QuIC assay. In the present review, we provide an overview on the different types of PrP substrates (FL and truncated forms), recapitulate the production and purification process of different rec PrP substrates, and discuss the diagnostic value of CSF RT-QuIC in human prion disease diagnostics. |
format | Online Article Text |
id | pubmed-10113290 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-101132902023-04-20 Role of different recombinant PrP substrates in the diagnostic accuracy of the CSF RT-QuIC assay in Creutzfeldt-Jakob disease Da Silva Correia, Susana Margarida Schmitz, Matthias Fischer, Andre Hermann, Peter Zerr, Inga Cell Tissue Res Review The development of the real-time quaking-induced conversion (RT-QuIC), an in vitro protein misfolding amplification assay, was an innovation in the scientific field of protein misfolding diseases. In prion diseases, these types of assays imitate the pathological conversion of the cellular prion protein (PrP(C)) into a protease-resistant and/or amyloid form of PrP, called PrP resistant (PrP(Res)). The RT-QuIC is an automatic assay system based on real-time measuring of thioflavin-T (Th-T) incorporation into amyloid fibrils using shaking for disaggregation. It has already been applied in diagnostics, drug pre-screening, and to distinguish between different prion strains. The seeded conversion efficiency and the diagnostic accuracy of the RT-QuIC assay strongly depend on the kind of recombinant PrP (rec PrP) substrate. The DNA sequences of different substrates may originate from different species, such as human, bank vole, and hamster, or from a combination of two species, e.g., hamster-sheep chimera. In routine use, either full-length (FL) or truncated substrates are applied which can accelerate the conversion reaction, e.g., to a more sensitive version of RT-QuIC assay. In the present review, we provide an overview on the different types of PrP substrates (FL and truncated forms), recapitulate the production and purification process of different rec PrP substrates, and discuss the diagnostic value of CSF RT-QuIC in human prion disease diagnostics. Springer Berlin Heidelberg 2022-12-20 2023 /pmc/articles/PMC10113290/ /pubmed/36536226 http://dx.doi.org/10.1007/s00441-022-03715-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Da Silva Correia, Susana Margarida Schmitz, Matthias Fischer, Andre Hermann, Peter Zerr, Inga Role of different recombinant PrP substrates in the diagnostic accuracy of the CSF RT-QuIC assay in Creutzfeldt-Jakob disease |
title | Role of different recombinant PrP substrates in the diagnostic accuracy of the CSF RT-QuIC assay in Creutzfeldt-Jakob disease |
title_full | Role of different recombinant PrP substrates in the diagnostic accuracy of the CSF RT-QuIC assay in Creutzfeldt-Jakob disease |
title_fullStr | Role of different recombinant PrP substrates in the diagnostic accuracy of the CSF RT-QuIC assay in Creutzfeldt-Jakob disease |
title_full_unstemmed | Role of different recombinant PrP substrates in the diagnostic accuracy of the CSF RT-QuIC assay in Creutzfeldt-Jakob disease |
title_short | Role of different recombinant PrP substrates in the diagnostic accuracy of the CSF RT-QuIC assay in Creutzfeldt-Jakob disease |
title_sort | role of different recombinant prp substrates in the diagnostic accuracy of the csf rt-quic assay in creutzfeldt-jakob disease |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113290/ https://www.ncbi.nlm.nih.gov/pubmed/36536226 http://dx.doi.org/10.1007/s00441-022-03715-9 |
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