Transthyretin: More than meets the eye

Fleming, Carolina E; Nunes, Ana V. M.; Sousa, Mónica Mendes

doi:10.1016/j.pneurobio.2009.07.007

Cited by 71 publications

(60 citation statements)

References 103 publications

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“…In plasma, thyroid-binding globulin normally binds 70% to 80% of thyroxine, transthyretin binds 10% to 15%, and the rest is bound to albumin. 3,24 Hence, these data suggest that T119M heterozygotes have increased total thyroxine levels attributable to an increased binding of thyroxine to transthyretin, but normal thyroid function. Results were similar after adjusting for age and sex by linear regression analysis (β-coefficient=18, corresponding to a mean increase in thyroxine of 18 nmol/L in heterozygotes versus noncarriers, P<0.0001; remaining P values, 0.57-0.73; data not shown).…”

Section: Ttr T119m Genotype and Plasma Transthyretinmentioning

confidence: 78%

“…1 Transthyretin is primarily synthesized in the liver, but is also produced in the choroid plexus. [1][2][3] Although the main function is to transport retinol-binding protein, transthyretin also transports ≈15% and 80% of thyroxine in blood and cerebrospinal fluid, respectively. 3 In both plasma and cerebrospinal fluid, transthyretin circulates as a tetramer comprising 4 identical subunits.…”

mentioning

confidence: 99%

“…[1][2][3] Although the main function is to transport retinol-binding protein, transthyretin also transports ≈15% and 80% of thyroxine in blood and cerebrospinal fluid, respectively. 3 In both plasma and cerebrospinal fluid, transthyretin circulates as a tetramer comprising 4 identical subunits. Destabilization of these tetramers leads to monomer misfolding and amyloidogenesis, a process that can be prevented by ligands, such as thyroxine, and by drugs that stabilize transthyretin tetramers.…”

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confidence: 99%

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Genetic Stabilization of Transthyretin, Cerebrovascular Disease, and Life Expectancy

Hornstrup

Frikke‐Schmidt

Nordestgaard

et al. 2013

ATVB

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Objective-Transthyretin can cause amyloidosis attributable to destabilization of transthyretin tetramers in plasma. We tested the hypothesis that genetic stabilization of transthyretin associates with reduced risk of vascular disease and increased life expectancy. Approach and Results-We included 68 602 participants from 2 prospective studies of the general population. We genotyped for 2 stabilizing genetic variants in the transthyretin gene (TTR), R104H and T119M, and determined the association of genotypes with plasma levels of transthyretin, measures of thyroid function, risk of vascular disease, and life expectancy. During a mean follow-up of 32 years, 10 636 participants developed vascular disease. We identified 321 heterozygotes for T119M (frequency, 0.47%); R104H was not detected. First, mean plasma transthyretin and thyroxine levels were increased by 17% (26 µg/mL) and 20% (19 nmol/L), respectively, in heterozygotes versus noncarriers (P=0.007 and P<0.0001), demonstrating functionality of this variant in the general population. Second, corresponding hazard ratios were 0.70 (95% confidence interval, 0.51-0.97) for all vascular diseases, 0.85 (0.59-1.23) for cardiovascular disease, 0.45 (0.25-0.81) for cerebrovascular disease, 0.47 (0.25-0.88) for ischemic cerebrovascular disease, and 0.31 (0.04-2.22) for hemorrhagic stroke. The cumulative incidence of cerebrovascular disease as a function of age was decreased in heterozygotes versus noncarriers (P=0.005). Third, median age at death from all causes, from vascular and cerebrovascular diseases, and after diagnosis of vascular disease, and median age at diagnosis of vascular disease, was increased by 5 to 10 years in heterozygotes versus noncarriers (P=0.002-0.05). Conclusions-These results are compatible with an association between genetic stabilization of transthyretin and decreased risk of cerebrovascular disease, and with increased life expectancy in the general population.

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Section: Ttr T119m Genotype and Plasma Transthyretinmentioning

confidence: 78%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Genetic Stabilization of Transthyretin, Cerebrovascular Disease, and Life Expectancy

Hornstrup

Frikke‐Schmidt

Nordestgaard

et al. 2013

ATVB

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“…Transthyretin has been shown to be a potential biomarker in pancreatic cancer [56] [57], but its association with multiple inflammatory disease processes may reduce its usefulness as a cancer biomarker [58]. Similarly, the use of fibrin and cofilin as LSCC biomarkers is limited by its non-specificity even though it is involved with various carcinogenic processes [59] [60].…”

Section: Discussionmentioning

confidence: 99%

Prognostic and Predictive Protein Biomarkers in Laryngeal Squamous Cell Carcinoma—A Systematic Review

Kwok¹,

Goodyear²

2015

IJOHNS

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Background: Despite recent advances in clinical management of laryngeal squamous cell carcinoma (LSCC), the overall 5-year survival continues to be poor. Consequently, biomarkers of treatment response will need to be identified. Proteomic strategies are one way to attempt to identify such biomarkers. Methods: The Medline, Embase and Cochrane Library databases were systematically searched until 1st March 2014 using the terms "larynx", "squamous cell carcinoma", "proteomic", and "biomarker". Articles which met inclusion criteria were assessed for the type of biomarker investigated, the proteomic technique used, and whether any validation had been performed. Results: Six studies identified biomarkers, including UCRP, ceramides, uPA, MT1-MMP, stratifin, transferrin, albumin, S100 calcium-binding protein A9, stathmin, enolase, PLAU, IGFBP7, MMP14, THBS1, and transthyretin. Transferrin was the only biomarker to appear in more than one study. Conclusions: Our review identified several potential biomarkers of outcome in LSCC. Well designed studies will need to further validate their use in the future.

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“…Intriguingly, altered TTR levels have been shown to have a role in depression and schizophrenia. 53,54 Thus, a marked decrease in TTR expression following GFP-CVB3 infection may provide a functional link between previous viral infection and these neurological disorders. 55,56 We further analyzed choroid plexus function following GFP-CVB3 infection by inspecting the expression levels of CAII.…”

Section: Discussionmentioning

confidence: 99%

Distinct neural stem cell tropism, early immune activation, and choroid plexus pathology following coxsackievirus infection in the neonatal central nervous system

Puccini

Ruller

Robinson

et al. 2014

Laboratory Investigation

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Coxsackievirus B3 (CVB3) and lymphocytic choriomeningitis virus (LCMV) are both neurotropic RNA viruses, which can establish a persistent infection and cause meningitis and encephalitis in the neonatal host. Utilizing our neonatal mouse model of infection, we evaluated the consequences of early viral infection upon the host central nervous system (CNS) by comparing CVB3 and LCMV infection. Both viruses expressed high levels of viral protein in the choroid plexus and subventricular zone (SVZ), a region of neurogenesis. LCMV infected a greater number of cells in the SVZ and targeted both nestin þ (neural progenitor cell marker) and olig2 þ (glial progenitor marker) cells at a relatively equal proportion. In contrast, CVB3 preferentially infected nestin þ cells within the SVZ. Microarray analysis revealed differential kinetics and unique host gene expression changes for each infection. MHC class I gene expression, several developmental-related Hox genes, and transthyretin (TTR), a protein secreted in the cerebrospinal fluid by the choroid plexus, were specifically downregulated following CVB3 infection. Also, we identified severe pathology in the choroid plexus of CVB3-infected animals at 48 h post infection accompanied by a decrease in the level of TTR and carbonic anhydrase II. These results demonstrate broader neural progenitor and stem cell (NPSC) tropism for LCMV in the neonatal CNS, whereas CVB3 targeted a more specific subset of NPSCs, stimulated a distinct early immune response, and induced significant acute damage in the choroid plexus.

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Transthyretin: More than meets the eye

Cited by 71 publications

References 103 publications

Genetic Stabilization of Transthyretin, Cerebrovascular Disease, and Life Expectancy

Genetic Stabilization of Transthyretin, Cerebrovascular Disease, and Life Expectancy

Prognostic and Predictive Protein Biomarkers in Laryngeal Squamous Cell Carcinoma—A Systematic Review

Distinct neural stem cell tropism, early immune activation, and choroid plexus pathology following coxsackievirus infection in the neonatal central nervous system

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