Undiscovered roles for transthyretin: from a transporter protein to a new therapeutic target for Alzheimer's disease

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 bindin...

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Detalles Bibliográficos
Autores: Gião, Tiago, Saavedra, Joana, Cotrina, Ellen, Quintana, Jordi, Llop, Jordi, Arsequell, Gemma, Cardoso, Isabel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/44916
Acceso en línea:http://hdl.handle.net/10230/44916
http://dx.doi.org/10.3390/ijms21062075
Access Level:acceso abierto
Palabra clave:Alzheimer’s disease
TTR tetrameric stability
Amyloid diseases
Angiogenesis
Blood–brain barrier
Cerebrospinal fluid protein
Neuroprotection
Transport protein
Transthyretin
Descripción
Sumario: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 Aβ 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.