Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 78, Issue 17-18, Pages 6105-6117Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-021-03899-3
Keywords
Transthyretin; Neuroprotection; Neuronal health; Cell metabolism; Proliferation
Categories
Funding
- FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020
- Portuguese funds through FCT - Fundacao Para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior [POCI-010145-FEDER-028336 (PTDC/MED-NEU/28336/2017), PTDC/MED-NEU/28336/2017, IF/00902/2015, SFRH/BD/116343/2016]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/116343/2016, PTDC/MED-NEU/28336/2017] Funding Source: FCT
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TTR is an extracellular protein involved in transporting thyroxin and retinol, but can also lead to amyloidosis. Recent studies show novel cellular activities of TTR, suggesting potential impacts on brain health, cellular fate, and metabolism beyond its known carrier functions.
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.
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