The role of transthyretin in cell biology: impact on human pathophysiology

Transthyretin (TTR) is an extracellular protein mainly produced in the liver and choroid plexus, with a well-stablished role in the transport of thyroxin and retinol throughout the body and brain. TTR is prone to aggregation, as both wild-type and mutated forms of the protein can lead to the accumul...

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Published in:Cellular and molecular life sciences : CMLS 2021-09, Vol.78 (17-18), p.6105-6117
Main Authors: Magalhães, Joana, Eira, Jessica, Liz, Márcia Almeida
Format: Article
Language:English
Subjects:
Amyloid
Amyloidosis
Amyloidosis - etiology
Amyloidosis - metabolism
Angiogenesis
Biochemistry
Biology
Biomedical and Life Sciences
Biomedicine
Brain
Cell Biology
Central Nervous System - metabolism
Choroid plexus
Humans
Intracellular signalling
Life Sciences
Literature reviews
Metabolism
Molecular modelling
Neurons - cytology
Neurons - metabolism
Prealbumin - chemistry
Prealbumin - genetics
Prealbumin - metabolism
Protein Aggregates - physiology
Proteins
Reactive Oxygen Species - metabolism
Review
Thyroxine
Thyroxine - chemistry
Thyroxine - metabolism
Transthyretin
Vitamin A
Vitamin A - chemistry
Vitamin A - metabolism
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Summary:Transthyretin (TTR) is an extracellular protein mainly produced in the liver and choroid plexus, with a well-stablished role in the transport of thyroxin and retinol throughout the body and brain. TTR is prone to aggregation, as both wild-type and mutated forms of the protein can lead to the accumulation of amyloid deposits, resulting in a disease called TTR amyloidosis. Recently, novel activities for TTR in cell biology have emerged, ranging from neuronal health preservation in both central and peripheral nervous systems, to cellular fate determination, regulation of proliferation and metabolism. Here, we review the novel literature regarding TTR new cellular effects. We pinpoint TTR as major player on brain health and nerve biology, activities that might impact on nervous systems pathologies, and assign a new link between TTR and angiogenesis and cancer. We also explore the molecular mechanisms underlying TTR activities at the cellular level, and suggest that these might go beyond its most acknowledged carrier functions and include interaction with receptors and activation of intracellular signaling pathways.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-021-03899-3