Undiscovered roles for transthyretin: From a transporter protein to a new therapeutic target for Alzheimer’s disease
Autor(a) principal: | |
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Data de Publicação: | 2020 |
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/10216/142502 |
Resumo: | Transthyretin (TTR), an homotetrameric protein mainly synthesized by the liver and the choroid plexus, and secreted into the blood and the cerebrospinal fluid, respectively, has been specially acknowledged for its functions as a transporter protein of thyroxine and retinol (the latter through binding to the retinol-binding protein), in these fluids. Still, this protein has managed to stay in the spotlight as it has been assigned new and varied functions. In this review, we cover knowledge on novel TTR functions and the cellular pathways involved, spanning from neuroprotection to vascular events, while emphasizing its involvement in Alzheimer’s disease (AD). We describe details of TTR as an amyloid binding protein and discuss its interaction with the amyloid Aß peptides, and the proposed mechanisms underlying TTR neuroprotection in AD. We also present the importance of translating advances in the knowledge of the TTR neuroprotective role into drug discovery strategies focused on TTR as a new target in AD therapeutics. |
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7160 |
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Undiscovered roles for transthyretin: From a transporter protein to a new therapeutic target for Alzheimer’s diseaseTransthyretin (TTR), an homotetrameric protein mainly synthesized by the liver and the choroid plexus, and secreted into the blood and the cerebrospinal fluid, respectively, has been specially acknowledged for its functions as a transporter protein of thyroxine and retinol (the latter through binding to the retinol-binding protein), in these fluids. Still, this protein has managed to stay in the spotlight as it has been assigned new and varied functions. In this review, we cover knowledge on novel TTR functions and the cellular pathways involved, spanning from neuroprotection to vascular events, while emphasizing its involvement in Alzheimer’s disease (AD). We describe details of TTR as an amyloid binding protein and discuss its interaction with the amyloid Aß peptides, and the proposed mechanisms underlying TTR neuroprotection in AD. We also present the importance of translating advances in the knowledge of the TTR neuroprotective role into drug discovery strategies focused on TTR as a new target in AD therapeutics.MDPI20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/142502eng1661-659610.3390/ijms21062075Gião, TSaavedra, JCotrina, EQuintana, JLlop, JArsequell, GCardoso, Iinfo: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:RCAAP2023-11-29T14:46:39Zoai:repositorio-aberto.up.pt:10216/142502Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:08:13.886790Repositório 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 |
Undiscovered roles for transthyretin: From a transporter protein to a new therapeutic target for Alzheimer’s disease |
title |
Undiscovered roles for transthyretin: From a transporter protein to a new therapeutic target for Alzheimer’s disease |
spellingShingle |
Undiscovered roles for transthyretin: From a transporter protein to a new therapeutic target for Alzheimer’s disease Gião, T |
title_short |
Undiscovered roles for transthyretin: From a transporter protein to a new therapeutic target for Alzheimer’s disease |
title_full |
Undiscovered roles for transthyretin: From a transporter protein to a new therapeutic target for Alzheimer’s disease |
title_fullStr |
Undiscovered roles for transthyretin: From a transporter protein to a new therapeutic target for Alzheimer’s disease |
title_full_unstemmed |
Undiscovered roles for transthyretin: From a transporter protein to a new therapeutic target for Alzheimer’s disease |
title_sort |
Undiscovered roles for transthyretin: From a transporter protein to a new therapeutic target for Alzheimer’s disease |
author |
Gião, T |
author_facet |
Gião, T Saavedra, J Cotrina, E Quintana, J Llop, J Arsequell, G Cardoso, I |
author_role |
author |
author2 |
Saavedra, J Cotrina, E Quintana, J Llop, J Arsequell, G Cardoso, I |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Gião, T Saavedra, J Cotrina, E Quintana, J Llop, J Arsequell, G Cardoso, I |
description |
Transthyretin (TTR), an homotetrameric protein mainly synthesized by the liver and the choroid plexus, and secreted into the blood and the cerebrospinal fluid, respectively, has been specially acknowledged for its functions as a transporter protein of thyroxine and retinol (the latter through binding to the retinol-binding protein), in these fluids. Still, this protein has managed to stay in the spotlight as it has been assigned new and varied functions. In this review, we cover knowledge on novel TTR functions and the cellular pathways involved, spanning from neuroprotection to vascular events, while emphasizing its involvement in Alzheimer’s disease (AD). We describe details of TTR as an amyloid binding protein and discuss its interaction with the amyloid Aß peptides, and the proposed mechanisms underlying TTR neuroprotection in AD. We also present the importance of translating advances in the knowledge of the TTR neuroprotective role into drug discovery strategies focused on TTR as a new target in AD therapeutics. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z |
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/10216/142502 |
url |
https://hdl.handle.net/10216/142502 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1661-6596 10.3390/ijms21062075 |
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 |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
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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1799136007947288576 |