Transthyretin C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Overview
Transthyretin (TTR) is a homo-tetrameric protein which transports thyroxine in the plasma and cerebrospinal fluid and retinol (vitamin A) in the plasma. Many disease causing mutations in the protein have been reported, many of which cause complex dissociation and protein mis-assembly and deposition of toxic aggregates amyloid fibril formation [9]. These amyloidogenic mutants are linked to the development of pathological amyloidoses, including familial amyloid polyneuropathy (FAP) [1,3], familial amyloid cardiomyopathy (FAC) [5], amyloidotic vitreous opacities, carpal tunnel syndrome [7] and others. In old age, non-mutated TTR can also form pathological amyloid fibrils [10]. Pharmacological intervention to reduce or prevent TTR dissociation is being pursued as a therapeutic strategy. To date one small molecule kinetic stabilising molecule (tafamidis) has been approved for FAP, and is being evaluated in clinical trials for other TTR amyloidoses.
Targets
Targets of relevance to immunopharmacology are highlighted in blue
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TTR (transthyretin) C
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How to cite this family page
Database page citation:
Transthyretin. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=911.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Buneman OP, Faccenda E, Harding SD, Spedding M, Cidlowski JA, Fabbro D, Davenport AP, Striessnig J, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Introduction and Other Protein Targets. Br J Pharmacol. 180 Suppl 2:S1-22.
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Excess production and accumulation of TTR causes hereditary transthyretin-mediated amyloidosis. Two novel drugs are now approved to combat this disease: inotersen (Tegsedi®) [6] and patisiran (Onpattro®) [4]. Both of these drugs act to reduce the amount of TTR protein (both wild type and mutant) produced in the liver, but by slightly different mechanisms. Inotersen is an antisense oligonucleotide inhibitor of TTR synthesis, whereas patisiran is a double-stranded small interfering RNA (which targets a conserved sequence in the 3' UTR of mutant and wild-type TTR mRNA). Inotersen is administered subcutaneously, and patisiran is delivered by intravenous infusion in a lipid nanoparticle formulation.