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Transthyretin from discovery to now.
1Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. jacobr@bdg10.niddk.nih.gov
Clinical Chemistry and Laboratory Medicine
|January 30, 2003
Summary
Transthyretin (TTR) transports thyroid hormone and vitamin A. Genetic variants of TTR are linked to familial amyloidotic polyneuropathy, prompting research into preventing its pathological transformation.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Discovery of thyroxine-binding prealbumin (TBPA) in the 1950s and its role in thyroid hormone transport.
- Elucidation of TBPA's tetrameric structure, allosteric thyroxine-binding sites, and synthesis by choroid plexus cells.
- Identification of TBPA's dual function in transporting vitamin A via retinol-binding protein (RBP), leading to its renaming as transthyretin (TTR).
Discussion:
- The discovery of inherited TTR variants, some affecting hormone and RBP binding.
- The association of the majority of TTR variants with familial amyloidotic polyneuropathy (FAP).
- Investigation into the structural changes of mutated TTR from soluble to insoluble amyloid fibrils.
Key Insights:
- TTR's crucial roles in transporting thyroxine and vitamin A.
- TTR's genetic variations are implicated in serious diseases like FAP.
- Understanding TTR's structural dynamics is key to preventing amyloid formation.
Outlook:
- Exploring the molecular mechanisms behind TTR's pathological transformation into amyloid fibrils.
- Developing strategies to prevent the fibrillar aggregation of mutated TTR.
- Leveraging TTR's properties as a biomarker for malnutrition and chronic disease.