Genomes and Genes
Summary: A tetrameric protein, molecular weight between 50,000 and 70,000, consisting of 4 equal chains, and migrating on electrophoresis in 3 fractions more mobile than serum albumin. Its concentration ranges from 7 to 33 per cent in the serum, but levels decrease in liver disease.
- Bourgault S, Solomon J, Reixach N, Kelly J. Sulfated glycosaminoglycans accelerate transthyretin amyloidogenesis by quaternary structural conversion. Biochemistry. 2011;50:1001-15 pubmed publisher..This model raises the possibility that GAGs may play a protective role in human amyloid diseases by interacting with proteotoxic oligomers and promoting their association into less toxic amyloid fibrils. ..
- Saito M, Seo Y, Yano Y, Miki A, Yoshida M, Azuma T. Short-term reductions in non-protein respiratory quotient and prealbumin can be associated with the long-term deterioration of liver function after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. J Gastroenterol. 2012;47:704-14 pubmed publisher..Multivariate analyses showed that the non-protein respiratory quotient (npRQ) and prealbumin (preAlb) ratios (7 days after/before TACE) were independent determinants of Child's score deterioration (p = 0...
- Saraiva M, Magalhaes J, Ferreira N, Almeida M. Transthyretin deposition in familial amyloidotic polyneuropathy. Curr Med Chem. 2012;19:2304-11 pubmed..Current knowledge and hypotheses on the biology of TTR, mechanisms of TTR amyloid fibril formation, phenotypic consequences TTR amyloid deposition and pre-clinical models of the disease will be discussed. ..
- Hornstrup L, Frikke Schmidt R, Nordestgaard B, Tybjærg Hansen A. Genetic stabilization of transthyretin, cerebrovascular disease, and life expectancy. Arterioscler Thromb Vasc Biol. 2013;33:1441-7 pubmed publisher..002-0.05). 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. ..
- da Costa G, Gomes R, Guerreiro A, Mateus E, Monteiro E, Barroso E, et al. Beyond genetic factors in familial amyloidotic polyneuropathy: protein glycation and the loss of fibrinogen's chaperone activity. PLoS ONE. 2011;6:e24850 pubmed publisher..Hence, we propose that methylglyoxal glycation hampers the chaperone activity of fibrinogen, rendering TTR more prone to aggregation, amyloid formation and ultimately, disease. ..
- Coelho T, Maia L, da Silva A, Cruz M, Plante Bordeneuve V, Suhr O, et al. Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy. J Neurol. 2013;260:2802-14 pubmed publisher..Tafamidis also slowed neurologic impairment in patients previously given placebo, but treatment benefits were greater when tafamidis was begun earlier. ..
- Ribeiro Silva C, Gilberto S, Gomes R, Mateus E, Monteiro E, Barroso E, et al. The relative amounts of plasma transthyretin forms in familial transthyretin amyloidosis: a quantitative analysis by Fourier transform ion-cyclotron resonance mass spectrometry. Amyloid. 2011;18:191-9 pubmed publisher..Our results point to the involvement of additional non-genetic factors on the pathogenesis of this disease. ..
- Koike H, Tanaka F, Hashimoto R, Tomita M, Kawagashira Y, Iijima M, et al. Natural history of transthyretin Val30Met familial amyloid polyneuropathy: analysis of late-onset cases from non-endemic areas. J Neurol Neurosurg Psychiatry. 2012;83:152-8 pubmed publisher..However, once an initial symptom appeared, the chronological sequence of other clinical landmarks tended to be uniform, occurring within a relatively short time span. ..
- Li X, Buxbaum J. Transthyretin and the brain re-visited: is neuronal synthesis of transthyretin protective in Alzheimer's disease?. Mol Neurodegener. 2011;6:79 pubmed publisher..We have proposed a model which is consistent with most of the published data and current notions of AD pathogenesis and can serve as a hypothesis which can be tested. ..
- Pires R, Saraiva M, Damas A, Kellermayer M. Structure and assembly-disassembly properties of wild-type transthyretin amyloid protofibrils observed with atomic force microscopy. J Mol Recognit. 2011;24:467-76 pubmed publisher..Thus, WT TTR can form metastable filamentous aggregates that may represent an important transient state along the pathway towards the formation of cytotoxic TTR species. ..
- Pokrzywa M, Dacklin I, Vestling M, Hultmark D, Lundgren E, Cantera R. Uptake of aggregating transthyretin by fat body in a Drosophila model for TTR-associated amyloidosis. PLoS ONE. 2010;5:e14343 pubmed publisher..These findings suggest that the uptake of TTR from the circulation and its subsequent segregation into cytoplasmic quasi-crystalline arrays of nanospherules is part of a mechanism that neutralizes the toxic effect of TTR. ..
- Caccialanza R, Palladini G, Klersy C, Cereda E, Bonardi C, Quarleri L, et al. Serum prealbumin: an independent marker of short-term energy intake in the presence of multiple-organ disease involvement. Nutrition. 2013;29:580-2 pubmed publisherSerum prealbumin has a prognostic value in several diseases, but its serum levels can be influenced by different factors...
- Henze A, Espe K, Wanner C, Krane V, Raila J, Hocher B, et al. Transthyretin predicts cardiovascular outcome in hemodialysis patients with type 2 diabetes. Diabetes Care. 2012;35:2365-72 pubmed publisher..TTR was particularly useful in patients who were not identified to be at risk by BMI or albumin status. ..
- Xie Y, Zhao Y, Zhou J, Wang X. [Identification of a TTR gene mutation in a family with hereditary vitreous amyloidosis]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2012;29:13-5 pubmed publisher..The heterozygous Gly103Arg mutation of TTR gene may be related to the development of hereditary vitreous amyloidosis in this family. ..
- Clifford S, Bunker A, Jacobsen J, Roberts W. Age and gender specific pediatric reference intervals for aldolase, amylase, ceruloplasmin, creatine kinase, pancreatic amylase, prealbumin, and uric acid. Clin Chim Acta. 2011;412:788-90 pubmed publisher..Seven analytes; aldolase, amylase, ceruloplasmin, creatine kinase, pancreatic amylase, prealbumin and uric acid; were assayed on Roche Modular P analyzers using serum samples from 1765 children (867 females and ..
- Mortimer R, Landers K, Balakrishnan B, Li H, Mitchell M, Patel J, et al. Secretion and transfer of the thyroid hormone binding protein transthyretin by human placenta. Placenta. 2012;33:252-6 pubmed publisher..This may have important implications for materno-fetal transfer of thyroid hormones, retinol/retinol binding protein and xenobiotics (such as polychlorinated biphenyls) all of which bind to TTR. ..
- Sueyoshi T, Ueda M, Jono H, Irie H, Sei A, Ide J, et al. Wild-type transthyretin-derived amyloidosis in various ligaments and tendons. Hum Pathol. 2011;42:1259-64 pubmed publisher..In the future, such amyloid deposits may aid determination of the pathogenesis of ligament and tendon disorders in older patients...
- Zhou M, Huang C, Wysocki V. Surface-induced dissociation of ion mobility-separated noncovalent complexes in a quadrupole/time-of-flight mass spectrometer. Anal Chem. 2012;84:6016-23 pubmed publisher..This work highlights the potential of utilizing IM-SID to study quaternary structures of protein complexes and provides information that is complementary to our recently reported SID-IM approach. ..
- Kawai H, Ota H. Low perioperative serum prealbumin predicts early recurrence after curative pulmonary resection for non-small-cell lung cancer. World J Surg. 2012;36:2853-7 pubmed publisher..In this study we evaluated the perioperative nutritional status of the patients by measuring the serum level of prealbumin and analyzed the correlation between this factor and early recurrence...
- Liu J, Guo Y, Zhou C, Ye Y, Feng J, Yin F, et al. Clinical and histopathological features of familial amyloidotic polyneuropathy with transthyretin Val30Ala in a Chinese family. J Neurol Sci. 2011;304:83-6 pubmed publisher..These results indicate that the distribution of amyloid deposition, (i.e., heavy in the liver, testes and slight in the spleen), is a characteristic feature and reflects the severity of FAP with TTR Val30Ala. ..
- Noborn F, O Callaghan P, Hermansson E, Zhang X, Ancsin J, Damas A, et al. Heparan sulfate/heparin promotes transthyretin fibrillization through selective binding to a basic motif in the protein. Proc Natl Acad Sci U S A. 2011;108:5584-9 pubmed publisher..Heparin of low molecular weight (Klexane) did not demonstrate this effect. ..
- Lee E, Lee H, Kamli M, Pokharel S, Bhat A, Lee Y, et al. Depot-specific gene expression profiles during differentiation and transdifferentiation of bovine muscle satellite cells, and differentiation of preadipocytes. Genomics. 2012;100:195-202 pubmed publisher..Induction of CD36 and FABP4 expression in adipocyte-like cells and adipocytes may share a common pathway. ..
- Obici L, Cortese A, Lozza A, Lucchetti J, Gobbi M, Palladini G, et al. Doxycycline plus tauroursodeoxycholic acid for transthyretin amyloidosis: a phase II study. Amyloid. 2012;19 Suppl 1:34-6 pubmed publisher..These preliminary data indicate that the combination of Doxy-TUDCA stabilizes the disease for at least 1 year in the majority of patients with an acceptable toxicity profile. ..
- da Costa G, Guerreiro A, Correia C, Gomes R, Freire A, Monteiro E, et al. A non-invasive method based on saliva to characterize transthyretin in familial amyloidotic polyneuropathy patients using FT-ICR high-resolution MS. Proteomics Clin Appl. 2010;4:674-8 pubmed..A suitable non-invasive method was developed for monitoring the most important FAP biomarker in human saliva. ..
- Guerreiro A, da Costa G, Gomes R, Ribeiro Silva C, Gilberto S, Mateus E, et al. ?-Synuclein aggregation in the saliva of familial transthyretin amyloidosis: a potential biomarker. Amyloid. 2012;19:74-80 pubmed publisher..Since ?-synuclein plays a major role in several neurodegenerative disorders, assessing its oligomerization state in this fluid provides a non-invasive approach to survey these pathologies...
- Fujii T, Sutoh T, Morita H, Katoh T, Yajima R, Tsutsumi S, et al. Serum albumin is superior to prealbumin for predicting short-term recurrence in patients with operable colorectal cancer. Nutr Cancer. 2012;64:1169-73 pubmed publisherThe relationship between preoperative prealbumin and cancer survival has not been fully elucidated...
- Ferreira N, Saraiva M, Almeida M. Natural polyphenols inhibit different steps of the process of transthyretin (TTR) amyloid fibril formation. FEBS Lett. 2011;585:2424-30 pubmed publisher..Our studies, together with the safe toxicological profile of these phytochemicals may guide a novel pharmacotherapy for TTR-related amyloidosis targeting different steps in fibrillogenesis. ..
- Huang L, Li J, Yan J, Liu C, Wu M, Yan Y. Prealbumin is predictive for postoperative liver insufficiency in patients undergoing liver resection. World J Gastroenterol. 2012;18:7021-5 pubmed publisher..On univariate analysis, age ? 60 years and prealbumin < 170 mg/dL were found to be significantly correlated with postoperative liver insufficiency (P = 0...
- Zhang K, Liu L, Cheng X, Dong J, Geng Q, Zuo L. Low levels of vitamin C in dialysis patients is associated with decreased prealbumin and increased C-reactive protein. BMC Nephrol. 2011;12:18 pubmed publisher..And we also measured body mass index (BMI, calculated as weight/height(2)), Kt/V, serum albumin, serum prealbumin, high-sensitivity C-reactive protein (hsCRP), ferritin, hemoglobin...
- Coelho T, Maia L, Martins da Silva A, Waddington Cruz M, Plante Bordeneuve V, Lozeron P, et al. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology. 2012;79:785-92 pubmed publisher..Secondary outcomes demonstrated a significant delay in peripheral neurologic impairment with tafamidis, which was well tolerated over 18 months. ..
- Bulawa C, Connelly S, Devit M, Wang L, Weigel C, Fleming J, et al. Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade. Proc Natl Acad Sci U S A. 2012;109:9629-34 pubmed publisher..The crystal structure of tafamidis-bound TTR suggests that binding stabilizes the weaker dimer-dimer interface against dissociation, the rate-limiting step of amyloidogenesis. ..
- Sato T, Sako Y, Sho M, Momohara M, Suico M, Shuto T, et al. STT3B-dependent posttranslational N-glycosylation as a surveillance system for secretory protein. Mol Cell. 2012;47:99-110 pubmed publisher..Hence we postulate that STT3B-dependent posttranslational N-glycosylation is part of a triage-salvage system recognizing cryptic N-glycosylation sites of secretory proteins to preserve protein homeostasis. ..
- Wixner J, Obayashi K, Ando Y, Karling P, Anan I. Loss of gastric interstitial cells of Cajal in patients with hereditary transthyretin amyloidosis. Amyloid. 2013;20:99-106 pubmed publisher..173 and 0.099, respectively). A loss of gastrointestinal ICC may be an important factor for the digestive disturbances in hereditary TTR amyloidosis. ..
- Johnson S, Connelly S, Fearns C, Powers E, Kelly J. The transthyretin amyloidoses: from delineating the molecular mechanism of aggregation linked to pathology to a regulatory-agency-approved drug. J Mol Biol. 2012;421:185-203 pubmed publisher..Here we review the biophysical basis for the kinetic stabilization strategy and the structure-based drug design effort that led to this first-in-class pharmacologic agent. ..
- Lin M, Liu W, Tolan A, Aboulian A, Petrie B, Stabile B. Preoperative serum albumin but not prealbumin is an excellent predictor of postoperative complications and mortality in patients with gastrointestinal cancer. Am Surg. 2011;77:1286-9 pubmed..Whether serum albumin or prealbumin levels can better predict postoperative surgical complications and death remains unknown...
- Smith K, Herron B, Dowell Mesfin N, Wu H, Kim S, Shain W, et al. Knockdown of cortical transthyretin expression around implanted neural prosthetic devices using intraventricular siRNA injection in the brain. J Neurosci Methods. 2012;203:398-406 pubmed publisher..These data demonstrate the feasibility of using RNA interference to modulate the initial reactive cellular responses that occur in the brain following insertion of neural prosthetic devices. ..
- Long D, Zeng J, Wu L, Tang L, Wang H, Wang H. Vitreous amyloidosis in two large mainland Chinese kindreds resulting from transthyretin variant Lys35Thr and Leu55Arg. Ophthalmic Genet. 2012;33:28-33 pubmed publisher..To describe the clinical and pathological findings of two large mainland Chinese kindreds with vitreous amyloidosis and associated transthyretin mutation...
- Sekijima Y, Uchiyama S, Tojo K, Sano K, Shimizu Y, Imaeda T, et al. High prevalence of wild-type transthyretin deposition in patients with idiopathic carpal tunnel syndrome: a common cause of carpal tunnel syndrome in the elderly. Hum Pathol. 2011;42:1785-91 pubmed publisher..It is likely that many patients develop carpal tunnel syndrome as an initial symptom of senile systemic amyloidosis. ..
- Xie Q, Zhou Y, Xu Z, Yang Y, Kuang D, You H, et al. The ratio of CRP to prealbumin levels predict mortality in patients with hospital-acquired acute kidney injury. BMC Nephrol. 2011;12:30 pubmed publisher..However, only a few studies reported CRP, a marker of inflammation, albumin, prealbumin and cholesterol, markers of nutritional status were associated with the prognosis of AKI patients...
- Riaz S, Alam S, Srai S, Skinner V, Riaz A, Akhtar M. Proteomic identification of human urinary biomarkers in diabetes mellitus type 2. Diabetes Technol Ther. 2010;12:979-88 pubmed publisher..Assessment of the levels of these biomarkers will be helpful not only in early diagnosis but also in prognosis of diabetes mellitus type 2. ..
- Santos S, Lambertsen K, Clausen B, Akinc A, Alvarez R, Finsen B, et al. CSF transthyretin neuroprotection in a mouse model of brain ischemia. J Neurochem. 2010;115:1434-44 pubmed publisher..Our data suggest that in conditions of a compromised heat-shock response, CSF TTR contributes to control neuronal cell death, edema and inflammation, thereby influencing the survival of endangered neurons in cerebral ischemia. ..
- Ferreira N, Cardoso I, Domingues M, Vitorino R, Bastos M, Bai G, et al. Binding of epigallocatechin-3-gallate to transthyretin modulates its amyloidogenicity. FEBS Lett. 2009;583:3569-76 pubmed publisher..These findings together with the low toxicity of the compound raise the possibility of using EGCG in a therapeutic approach for familial amyloidotic polyneuropathy, the most frequent form of hereditary TTR amyloidosis. ..
- Llado L, Baliellas C, Casasnovas C, Ferrer I, Fabregat J, Ramos E, et al. Risk of transmission of systemic transthyretin amyloidosis after domino liver transplantation. Liver Transpl. 2010;16:1386-92 pubmed publisher..Sural nerve biopsy with EMG and clinical correlation is mandatory for confirming the disease. Indeed, other causes of neuropathy should be excluded. ..
- Buxbaum J, Reixach N. Transthyretin: the servant of many masters. Cell Mol Life Sci. 2009;66:3095-101 pubmed publisherTransthyretin (TTR) (formerly, thyroxine binding prealbumin) is an evolutionarily conserved serum and cerebrospinal fluid protein that transports holo-retinol-binding protein and thyroxine...
- Costa R, Goncalves A, Saraiva M, Cardoso I. Transthyretin binding to A-Beta peptide--impact on A-Beta fibrillogenesis and toxicity. FEBS Lett. 2008;582:936-42 pubmed publisher..Our results confirmed TTR as an A-Beta ligand and indicated the inhibition/disruption of A-Beta fibrils as a possible mechanism underlying the protective role of TTR in AD. ..
- Revesz T, Holton J, Lashley T, Plant G, Frangione B, Rostagno A, et al. Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies. Acta Neuropathol. 2009;118:115-30 pubmed publisher..In this review, the characteristic morphological features of the different CAAs is described and the implication of the biochemical, genetic and transgenic animal data for the pathogenesis of CAA is discussed. ..
- Mairal T, Nieto J, Pinto M, Almeida M, Gales L, Ballesteros A, et al. Iodine atoms: a new molecular feature for the design of potent transthyretin fibrillogenesis inhibitors. PLoS ONE. 2009;4:e4124 pubmed publisher..Biochemical and biophysical evidence confirms that iodine atoms can be an important design feature in the search for candidate drugs for TTR related amyloidosis. ..