Chemical Kinetic Strategies for High-Throughput Screening of Protein Aggregation Modulators
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/10216/122230 |
Resumo: | Insoluble aggregates staining positive to amyloid dyes are known histological hallmarks of different neurodegenerative disorders and of type II diabetes. Soluble oligomers are smaller assemblies whose formation prior to or concomitant with amyloid deposition has been associated to the processes of disease propagation and cell death. While the pathogenic mechanisms are complex and differ from disease to disease, both types of aggregates are important biological targets subject to intense investigation in academia and industry. Here we review recent advances in the fundamental understanding of protein aggregation that can be used on the development of anti-amyloid and anti-oligomerization drugs. Specifically, we pinpoint the chemical kinetic aspects that should be attended during the development of high-throughput screening assays and in the hit validation phase. The strategies here devised are expected to establish a connection between basic research and pharmaceutical innovation. |
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Chemical Kinetic Strategies for High-Throughput Screening of Protein Aggregation ModulatorsInsoluble aggregates staining positive to amyloid dyes are known histological hallmarks of different neurodegenerative disorders and of type II diabetes. Soluble oligomers are smaller assemblies whose formation prior to or concomitant with amyloid deposition has been associated to the processes of disease propagation and cell death. While the pathogenic mechanisms are complex and differ from disease to disease, both types of aggregates are important biological targets subject to intense investigation in academia and industry. Here we review recent advances in the fundamental understanding of protein aggregation that can be used on the development of anti-amyloid and anti-oligomerization drugs. Specifically, we pinpoint the chemical kinetic aspects that should be attended during the development of high-throughput screening assays and in the hit validation phase. The strategies here devised are expected to establish a connection between basic research and pharmaceutical innovation.20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/122230eng1861-472810.1002/asia.201801703Zsuzsa SárkányFernando RochaAna M. DamasSandra Macedo RibeiroPedro M. Martinsinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T13:36:25Zoai:repositorio-aberto.up.pt:10216/122230Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T23:43:39.443911Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Chemical Kinetic Strategies for High-Throughput Screening of Protein Aggregation Modulators |
title |
Chemical Kinetic Strategies for High-Throughput Screening of Protein Aggregation Modulators |
spellingShingle |
Chemical Kinetic Strategies for High-Throughput Screening of Protein Aggregation Modulators Zsuzsa Sárkány |
title_short |
Chemical Kinetic Strategies for High-Throughput Screening of Protein Aggregation Modulators |
title_full |
Chemical Kinetic Strategies for High-Throughput Screening of Protein Aggregation Modulators |
title_fullStr |
Chemical Kinetic Strategies for High-Throughput Screening of Protein Aggregation Modulators |
title_full_unstemmed |
Chemical Kinetic Strategies for High-Throughput Screening of Protein Aggregation Modulators |
title_sort |
Chemical Kinetic Strategies for High-Throughput Screening of Protein Aggregation Modulators |
author |
Zsuzsa Sárkány |
author_facet |
Zsuzsa Sárkány Fernando Rocha Ana M. Damas Sandra Macedo Ribeiro Pedro M. Martins |
author_role |
author |
author2 |
Fernando Rocha Ana M. Damas Sandra Macedo Ribeiro Pedro M. Martins |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Zsuzsa Sárkány Fernando Rocha Ana M. Damas Sandra Macedo Ribeiro Pedro M. Martins |
description |
Insoluble aggregates staining positive to amyloid dyes are known histological hallmarks of different neurodegenerative disorders and of type II diabetes. Soluble oligomers are smaller assemblies whose formation prior to or concomitant with amyloid deposition has been associated to the processes of disease propagation and cell death. While the pathogenic mechanisms are complex and differ from disease to disease, both types of aggregates are important biological targets subject to intense investigation in academia and industry. Here we review recent advances in the fundamental understanding of protein aggregation that can be used on the development of anti-amyloid and anti-oligomerization drugs. Specifically, we pinpoint the chemical kinetic aspects that should be attended during the development of high-throughput screening assays and in the hit validation phase. The strategies here devised are expected to establish a connection between basic research and pharmaceutical innovation. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019 2019-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/10216/122230 |
url |
https://hdl.handle.net/10216/122230 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1861-4728 10.1002/asia.201801703 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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