Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/51513 |
Resumo: | Polyglutamine (PolyQ) diseases are a group of neurodegenerative disorders caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the coding region of specific genes. This leads to the production of pathogenic proteins containing critically expanded tracts of glutamines. Although polyQ diseases are individually rare, the fact that these nine diseases are irreversibly progressive over 10 to 30 years, severely impairing and ultimately fatal, usually implicating the full-time patient support by a caregiver for long time periods, makes their economic and social impact quite significant. This has led several researchers worldwide to investigate the pathogenic mechanism(s) and therapeutic strategies for polyQ diseases. Although research in the field has grown notably in the last decades, we are still far from having an effective treatment to offer patients, and the decision of which compounds should be translated to the clinics may be very challenging. In this review, we provide a comprehensive and critical overview of the most recent drug discovery efforts in the field of polyQ diseases, including the most relevant findings emerging from two different types of approaches-hypothesis-based candidate molecule testing and hypothesis-free unbiased drug screenings. We hereby summarize and reflect on the preclinical studies as well as all the clinical trials performed to date, aiming to provide a useful framework for increasingly successful future drug discovery and development efforts. |
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Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Effortspolyglutamine diseasestherapeutic strategiespreclinical trialsclinical trialsCiências Médicas::Medicina ClínicaScience & TechnologyPolyglutamine (PolyQ) diseases are a group of neurodegenerative disorders caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the coding region of specific genes. This leads to the production of pathogenic proteins containing critically expanded tracts of glutamines. Although polyQ diseases are individually rare, the fact that these nine diseases are irreversibly progressive over 10 to 30 years, severely impairing and ultimately fatal, usually implicating the full-time patient support by a caregiver for long time periods, makes their economic and social impact quite significant. This has led several researchers worldwide to investigate the pathogenic mechanism(s) and therapeutic strategies for polyQ diseases. Although research in the field has grown notably in the last decades, we are still far from having an effective treatment to offer patients, and the decision of which compounds should be translated to the clinics may be very challenging. In this review, we provide a comprehensive and critical overview of the most recent drug discovery efforts in the field of polyQ diseases, including the most relevant findings emerging from two different types of approaches-hypothesis-based candidate molecule testing and hypothesis-free unbiased drug screenings. We hereby summarize and reflect on the preclinical studies as well as all the clinical trials performed to date, aiming to provide a useful framework for increasingly successful future drug discovery and development efforts.Project ON.2 SR&TD Integrated Program (NORTE-07-0124-FEDER-000021), co-funded by North Portugal Regional Operational Program (ON.2-O Novo Norte), under the National Strategic Reference Framework, through the European Regional Development Fund (ERDF) and also supported by Fundação para a Ciência e Tecnologia through the project POCI-01-0145-FEDER-016818 (PTDC/NEU-NMC/3648/2014)info:eu-repo/semantics/publishedVersionWileyUniversidade do MinhoEsteves, SofiaSilva, Sara Carina DuarteMaciel, P.20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/51513engEsteves, S., Duarte‐Silva, S., & Maciel, P. (2017). Discovery of therapeutic approaches for polyglutamine diseases: a summary of recent efforts. Medicinal research reviews, 37(4), 860-9060198-63251098-112810.1002/med.2142527870126http://onlinelibrary.wiley.com/doi/10.1002/med.21425/fullinfo: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:RCAAP2023-07-21T12:12:48Zoai:repositorium.sdum.uminho.pt:1822/51513Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:04:47.779558Repositório 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 |
Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts |
title |
Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts |
spellingShingle |
Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts Esteves, Sofia polyglutamine diseases therapeutic strategies preclinical trials clinical trials Ciências Médicas::Medicina Clínica Science & Technology |
title_short |
Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts |
title_full |
Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts |
title_fullStr |
Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts |
title_full_unstemmed |
Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts |
title_sort |
Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts |
author |
Esteves, Sofia |
author_facet |
Esteves, Sofia Silva, Sara Carina Duarte Maciel, P. |
author_role |
author |
author2 |
Silva, Sara Carina Duarte Maciel, P. |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Esteves, Sofia Silva, Sara Carina Duarte Maciel, P. |
dc.subject.por.fl_str_mv |
polyglutamine diseases therapeutic strategies preclinical trials clinical trials Ciências Médicas::Medicina Clínica Science & Technology |
topic |
polyglutamine diseases therapeutic strategies preclinical trials clinical trials Ciências Médicas::Medicina Clínica Science & Technology |
description |
Polyglutamine (PolyQ) diseases are a group of neurodegenerative disorders caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the coding region of specific genes. This leads to the production of pathogenic proteins containing critically expanded tracts of glutamines. Although polyQ diseases are individually rare, the fact that these nine diseases are irreversibly progressive over 10 to 30 years, severely impairing and ultimately fatal, usually implicating the full-time patient support by a caregiver for long time periods, makes their economic and social impact quite significant. This has led several researchers worldwide to investigate the pathogenic mechanism(s) and therapeutic strategies for polyQ diseases. Although research in the field has grown notably in the last decades, we are still far from having an effective treatment to offer patients, and the decision of which compounds should be translated to the clinics may be very challenging. In this review, we provide a comprehensive and critical overview of the most recent drug discovery efforts in the field of polyQ diseases, including the most relevant findings emerging from two different types of approaches-hypothesis-based candidate molecule testing and hypothesis-free unbiased drug screenings. We hereby summarize and reflect on the preclinical studies as well as all the clinical trials performed to date, aiming to provide a useful framework for increasingly successful future drug discovery and development efforts. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 2017-01-01T00:00:00Z |
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 |
http://hdl.handle.net/1822/51513 |
url |
http://hdl.handle.net/1822/51513 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Esteves, S., Duarte‐Silva, S., & Maciel, P. (2017). Discovery of therapeutic approaches for polyglutamine diseases: a summary of recent efforts. Medicinal research reviews, 37(4), 860-906 0198-6325 1098-1128 10.1002/med.21425 27870126 http://onlinelibrary.wiley.com/doi/10.1002/med.21425/full |
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.publisher.none.fl_str_mv |
Wiley |
publisher.none.fl_str_mv |
Wiley |
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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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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