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A Narrative Review of the Role of Transthyretin in Health and Disease

Transthyretin (TTR) is a tetrameric transport protein highly conserved through vertebrate evolution and synthesized in the liver, choroid plexus, and retinal pigment epithelium. TTR transports the thyroid hormone thyroxine and the retinol-binding protein (RBP) bound to retinol (vitamin A). Mutations...

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Autores principales: Liz, Marcia Almeida, Coelho, Teresa, Bellotti, Vittorio, Fernandez-Arias, Maria Isabel, Mallaina, Pablo, Obici, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606379/
https://www.ncbi.nlm.nih.gov/pubmed/33001386
http://dx.doi.org/10.1007/s40120-020-00217-0
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author Liz, Marcia Almeida
Coelho, Teresa
Bellotti, Vittorio
Fernandez-Arias, Maria Isabel
Mallaina, Pablo
Obici, Laura
author_facet Liz, Marcia Almeida
Coelho, Teresa
Bellotti, Vittorio
Fernandez-Arias, Maria Isabel
Mallaina, Pablo
Obici, Laura
author_sort Liz, Marcia Almeida
collection PubMed
description Transthyretin (TTR) is a tetrameric transport protein highly conserved through vertebrate evolution and synthesized in the liver, choroid plexus, and retinal pigment epithelium. TTR transports the thyroid hormone thyroxine and the retinol-binding protein (RBP) bound to retinol (vitamin A). Mutations in TTR are associated with inherited transthyretin amyloidosis (ATTRv), a progressive, debilitating disease that is ultimately fatal and is characterized by misfolding of TTR and aggregation as amyloid fibrils, predominantly leading to cardiomyopathy or polyneuropathy depending on the particular TTR mutation. Transthyretin amyloid cardiomyopathy can also occur as an age-related disease caused by misfolding of wild-type TTR. Apart from its transport role, little is known about possible additional physiological functions of TTR. Evidence from animal model systems in which TTR has been disrupted via gene knockout is adding to our cumulative understanding of TTR function. There is growing evidence that TTR may have a role in neuroprotection and promotion of neurite outgrowth in response to injury. Here, we review the literature describing potential roles of TTR in neurobiology and in the pathophysiology of diseases other than ATTR amyloidosis. A greater understanding of these processes may also contribute to further clarification of the pathology of ATTR and the effects of potential therapies for TTR-related conditions.
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spelling pubmed-76063792020-11-10 A Narrative Review of the Role of Transthyretin in Health and Disease Liz, Marcia Almeida Coelho, Teresa Bellotti, Vittorio Fernandez-Arias, Maria Isabel Mallaina, Pablo Obici, Laura Neurol Ther Review Transthyretin (TTR) is a tetrameric transport protein highly conserved through vertebrate evolution and synthesized in the liver, choroid plexus, and retinal pigment epithelium. TTR transports the thyroid hormone thyroxine and the retinol-binding protein (RBP) bound to retinol (vitamin A). Mutations in TTR are associated with inherited transthyretin amyloidosis (ATTRv), a progressive, debilitating disease that is ultimately fatal and is characterized by misfolding of TTR and aggregation as amyloid fibrils, predominantly leading to cardiomyopathy or polyneuropathy depending on the particular TTR mutation. Transthyretin amyloid cardiomyopathy can also occur as an age-related disease caused by misfolding of wild-type TTR. Apart from its transport role, little is known about possible additional physiological functions of TTR. Evidence from animal model systems in which TTR has been disrupted via gene knockout is adding to our cumulative understanding of TTR function. There is growing evidence that TTR may have a role in neuroprotection and promotion of neurite outgrowth in response to injury. Here, we review the literature describing potential roles of TTR in neurobiology and in the pathophysiology of diseases other than ATTR amyloidosis. A greater understanding of these processes may also contribute to further clarification of the pathology of ATTR and the effects of potential therapies for TTR-related conditions. Springer Healthcare 2020-10-01 /pmc/articles/PMC7606379/ /pubmed/33001386 http://dx.doi.org/10.1007/s40120-020-00217-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial 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-nc/4.0/.
spellingShingle Review
Liz, Marcia Almeida
Coelho, Teresa
Bellotti, Vittorio
Fernandez-Arias, Maria Isabel
Mallaina, Pablo
Obici, Laura
A Narrative Review of the Role of Transthyretin in Health and Disease
title A Narrative Review of the Role of Transthyretin in Health and Disease
title_full A Narrative Review of the Role of Transthyretin in Health and Disease
title_fullStr A Narrative Review of the Role of Transthyretin in Health and Disease
title_full_unstemmed A Narrative Review of the Role of Transthyretin in Health and Disease
title_short A Narrative Review of the Role of Transthyretin in Health and Disease
title_sort narrative review of the role of transthyretin in health and disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606379/
https://www.ncbi.nlm.nih.gov/pubmed/33001386
http://dx.doi.org/10.1007/s40120-020-00217-0
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