Publicação
Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts
| 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. |
|---|---|
| Autores principais: | Esteves, Sofia |
| Outros Autores: | Silva, Sara Carina Duarte; Maciel, P. |
| Assunto: | polyglutamine diseases therapeutic strategies preclinical trials clinical trials Ciências Médicas::Medicina Clínica |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1867438442284056576 |
|---|---|
| author | Esteves, Sofia |
| author2 | Silva, Sara Carina Duarte Maciel, P. |
| author2_role | author author |
| author_facet | Esteves, Sofia Silva, Sara Carina Duarte Maciel, P. |
| author_role | author |
| contributor_name_str_mv | RepositóriUM - Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Esteves, Sofia\"},{\"Person.name\":\"Silva, Sara Carina Duarte\"},{\"Person.name\":\"Maciel, P.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RepositóriUM - Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Esteves, Sofia Silva, Sara Carina Duarte Maciel, P. |
| datacite.date.Accepted.fl_str_mv | 2017-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2018-03-05T12:03:21Z |
| datacite.date.embargoed.fl_str_mv | 2018-03-05T12:03:21Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | polyglutamine diseases therapeutic strategies preclinical trials clinical trials Ciências Médicas::Medicina Clínica |
| datacite.titles.title.fl_str_mv | Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts |
| dc.contributor.none.fl_str_mv | RepositóriUM - Universidade do Minho |
| dc.creator.none.fl_str_mv | Esteves, Sofia Silva, Sara Carina Duarte Maciel, P. |
| dc.date.Accepted.fl_str_mv | 2017-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2018-03-05T12:03:21Z |
| dc.date.embargoed.fl_str_mv | 2018-03-05T12:03:21Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/51513 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Wiley |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | polyglutamine diseases therapeutic strategies preclinical trials clinical trials Ciências Médicas::Medicina Clínica |
| dc.title.fl_str_mv | Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/1c157a56-284b-45c0-b9a2-29db9be48101/download |
| id | rum_6b615dfd9e8cb5546058e51abebfb1f9 |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/51513 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/51513 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Esteves, Sofia Silva, Sara Carina Duarte Maciel, P. |
| publishDate | 2017 |
| publisher.none.fl_str_mv | Wiley |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engWileyporPolyglutamine (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.application/pdfporDiscovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent EffortsEsteves, SofiaSilva, Sara Carina DuarteMaciel, P.HostingInstitutionOrganizationalRepositóriUM - Universidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptCITATIONEsteves, S., Duarte‐Silva, S., & Maciel, P. (2017). Discovery of therapeutic approaches for polyglutamine diseases: a summary of recent efforts. Medicinal research reviews, 37(4), 860-906PMID27870126ISSNIsPartOf0198-6325EISSNIsPartOf1098-1128DOIIsPartOf10.1002/med.214252018-03-05T12:03:21Z20172018-01-26T09:20:17Z2017-01-01T00:00:00ZHandlehttps://hdl.handle.net/1822/51513http://purl.org/coar/access_right/c_abf2open accesspolyglutamine diseasestherapeutic strategiespreclinical trialsclinical trialshttp://www.oecd.org/science/inno/38235147.pdfFields of Science and Technology (FOS)Ciências Médicas::Medicina Clínica1146748 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/1c157a56-284b-45c0-b9a2-29db9be48101/download |
| 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 |
| status | SINGLETON |
| subject.fl_str_mv | polyglutamine diseases therapeutic strategies preclinical trials clinical trials |
| subject.other.fl_str_mv | Ciências Médicas::Medicina Clínica |
| title | 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_short | 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 |
| topic | polyglutamine diseases therapeutic strategies preclinical trials clinical trials Ciências Médicas::Medicina Clínica |
| topic_facet | polyglutamine diseases therapeutic strategies preclinical trials clinical trials Ciências Médicas::Medicina Clínica |
| url | https://hdl.handle.net/1822/51513 |
| visible | 1 |