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Scandinavian Journal of Immunology Feb 1985A prealbumin (PA)-like protein was demonstrated in amyloid fibrils both from a patient with senile systemic amyloidosis (SSA) and from a patient in northern Sweden with...
A prealbumin (PA)-like protein was demonstrated in amyloid fibrils both from a patient with senile systemic amyloidosis (SSA) and from a patient in northern Sweden with familial amyloidotic polyneuropathy (FAP). The investigated properties of this protein were similar in the two types of fibrils. The protein had molecular weight, antigenic determinants, and at least one cysteinyl residue in common with the subunit of normal PA. In contrast to normal PA, it contained disulphide-linked subunits and was to some extent bound to the fibril via the cysteinyl residues. The noncovalent forces between its subunits were weaker than in normal PA. It constituted part of the previously described AScl protein of the SSA fibrils. Proteins with lower molecular weight than the PA monomer were major proteins in both SSA and FAP fibrils. These proteins had similar properties in the two kinds of fibril and may be derived from PA. PA in serum from Swedish patients with FAP and SSA was normal with regard to the isoelectric pH of the monomers and tetramers.
Topics: Adult; Aged; Aging; Amyloidosis; Antigen-Antibody Reactions; Chemical Phenomena; Chemistry; Electrophoresis, Polyacrylamide Gel; Humans; Isoelectric Focusing; Male; Middle Aged; Molecular Weight; Peripheral Nervous System Diseases; Prealbumin; Serum Amyloid A Protein; Sweden
PubMed: 2983415
DOI: 10.1111/j.1365-3083.1985.tb01412.x -
Trends in Neurosciences Mar 1989Amyloidosis has received considerable attention recently because of its association with Alzheimer's disease. Actually, the amyloid in the cortical plaques, which is... (Review)
Review
Amyloidosis has received considerable attention recently because of its association with Alzheimer's disease. Actually, the amyloid in the cortical plaques, which is characteristic of Alzheimer's disease, is a localized form of amyloid deposition. Although intracranial vascular amyloid deposits which contain the A4 or beta-protein are usually associated with Alzheimer's disease, deposition of this amyloid fibril substance in other organs of the body has not been described. Much less attention has been paid to amyloid involvement of the PNS which is a fascinating subject in itself and is the subject of this review.
Topics: Amyloidosis; Heterozygote; Humans; Peripheral Nervous System Diseases; Prealbumin
PubMed: 2469222
DOI: 10.1016/0166-2236(89)90162-8 -
Biomolecular Concepts Mar 2014Transthyretin is a highly conserved homotetrameric protein, mainly synthetized by the liver and the choroid plexus of brain. The carrier role of TTR is well-known;... (Review)
Review
Transthyretin is a highly conserved homotetrameric protein, mainly synthetized by the liver and the choroid plexus of brain. The carrier role of TTR is well-known; however, many other functions have emerged, namely in the nervous system. Behavior, cognition, neuropeptide amidation, neurogenesis, nerve regeneration, axonal growth and 14-3-3ζ metabolism are some of the processes where TTR has an important role. TTR aggregates are responsible for many amyloidosis such as familial amyloidotic polyneuropathy and cardiomyopathy. Normal TTR can also aggregate and deposit in the heart of old people and in preeclampsia placental tissue. Differences in TTR levels have been found in several neuropathologies, but its neuroprotective role, until now, was described in ischemia and Alzheimer's disease. The aim of this review is to stress the relevance of TTR, besides its well-known role on transport of thyroxine and retinol-binding protein.
Topics: Animals; Choroid Plexus; Humans; Liver; Nervous System Diseases; Prealbumin; Retinol-Binding Proteins; Thyroxine
PubMed: 25372741
DOI: 10.1515/bmc-2013-0038 -
Cellular and Molecular Life Sciences :... Oct 2009Transthyretin (TTR) (formerly, thyroxine binding prealbumin) is an evolutionarily conserved serum and cerebrospinal fluid protein that transports holo-retinol-binding... (Review)
Review
Transthyretin (TTR) (formerly, thyroxine binding prealbumin) is an evolutionarily conserved serum and cerebrospinal fluid protein that transports holo-retinol-binding protein and thyroxine. Its serum concentration has been widely used to assess clinical nutritional status. It is also well known that wild-type transthyretin and approximately 100 different mutants give rise to a variety of forms of systemic amyloid deposition. It has been suspected and recently established that TTR can suppress the Alzheimer's disease phenotype in transgenic animal models of cerebral Abeta deposition. Thus, while TTR is a systemic amyloid precursor, in the brain it seems to have an anti-amyloidogenic effect. TTR is found in other organs as a result of local synthesis or transport, suggesting that it may have other, as yet undiscovered, functions. It is possible that its capacity to bind many classes of compounds allows it to serve as an endogenous detoxifier of molecules with potential pathologic effects.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain; Disease Models, Animal; Eye; Humans; Mice; Pancreas; Plasma; Prealbumin
PubMed: 19644733
DOI: 10.1007/s00018-009-0109-0 -
Circulation Nov 2022
Topics: Humans; Prealbumin; Amyloidosis; Cognition
PubMed: 36441817
DOI: 10.1161/CIRCULATIONAHA.122.062532 -
Acta Paediatrica Scandinavica Jul 1979
Topics: Humans; Infant, Newborn; Infant, Small for Gestational Age; Prealbumin; Serum Albumin
PubMed: 463545
DOI: 10.1111/j.1651-2227.1979.tb05065.x -
Brain and Nerve = Shinkei Kenkyu No... Jul 2014Amyloidosis refers to disorders that cause organ failure due to amyloid deposition. Deposited amyloid is clearly stained by Congo red and is detected by apple-green...
Amyloidosis refers to disorders that cause organ failure due to amyloid deposition. Deposited amyloid is clearly stained by Congo red and is detected by apple-green birefringence under polarized light. Amyloid fibril proteins are very stable, but several recent studies have revealed that amyloid deposition and the clearance of fibrils cause the steady turnover of deposited amyloid proteins. Therefore, in several amyloidosis disorders, especially primary AL, reactive AA, and transthyretin-related amyloidosis, effective therapies are expected to cause the regression of tissue-deposited amyloid.
Topics: Amyloid; Amyloidosis; Humans; Liver Transplantation; Prealbumin; Protein Folding; Protein Structure, Secondary
PubMed: 24998817
DOI: No ID Found -
Placenta Jul 2013Since its discovery, transthyretin (TTR) has been regarded as an important hepatically derived protein carrier of thyroid hormones and retinol in blood. However, in more... (Review)
Review
Since its discovery, transthyretin (TTR) has been regarded as an important hepatically derived protein carrier of thyroid hormones and retinol in blood. However, in more recent years it has been shown that TTR has other important functions. TTR is abundant in cerebrospinal fluid, where it may be involved in transport of thyroid hormones into the brain. TTR derived amyloid is associated with diseases such as senile systemic amyloidosis, familial amyloid polyneuropathy and familial amyloid cardiomyopathy. Recently, synthesis, secretion and uptake of TTR by human placenta have been reported. TTR appears to play an important role in the delivery of maternal thyroid hormone to the developing fetus. This review explores the various proposed roles of TTR and more recent findings on TTR synthesis and expression in the placenta.
Topics: Female; Humans; Placenta; Prealbumin; Pregnancy
PubMed: 23664144
DOI: 10.1016/j.placenta.2013.04.013 -
Progress in Neurobiology Nov 2009Transthyretin (TTR) is a plasma protein mostly known for being the transporter of thyroxine and retinol. When mutated, TTR is also well-described as the cause of... (Review)
Review
Transthyretin (TTR) is a plasma protein mostly known for being the transporter of thyroxine and retinol. When mutated, TTR is also well-described as the cause of familial amyloid polyneuropathy, a neurodegenerative lethal disorder characterized by systemic deposition of TTR amyloid fibrils, particularly in the peripheral nervous system. Recent studies have determined that besides its carrier properties, TTR is an important protein in peripheral and central nervous system physiology, namely by participating in behavior, in the maintenance of normal cognitive processes during ageing, amidated neuropeptide processing and nerve regeneration. Additionally, it has been proposed that TTR is neuroprotective in Alzheimer's disease, by preventing the formation of amyloid beta fibrils. With the advent of powerful screening techniques, TTR has also been linked to a number of other pathological conditions, including Parkinson's disease, schizophrenia, depression, among others. These associations, together with the recently unraveled nervous system-related functions, suggest that the relevance of TTR in physiology, particularly in neurobiology, is undervalued and that additional research in this field is needed. The aim of this review is to integrate in a critical perspective the current scattered knowledge concerning TTR most and less acknowledged functions and its association with several neuropathologies.
Topics: Amyloid beta-Peptides; Animals; Disease Models, Animal; Humans; Mental Disorders; Mice; Nervous System; Nervous System Diseases; Prealbumin
PubMed: 19665514
DOI: 10.1016/j.pneurobio.2009.07.007 -
Drugs of Today (Barcelona, Spain : 1998) May 2012Tafamidis meglumine (Vyndaqel®, Pfizer) is a novel, first-in-class drug for the treatment of transthyretin familial amyloid polyneuropathy (TTR-FAP), a rare... (Review)
Review
Tafamidis meglumine (Vyndaqel®, Pfizer) is a novel, first-in-class drug for the treatment of transthyretin familial amyloid polyneuropathy (TTR-FAP), a rare neurodegenerative disorder characterized by progressive sensory, motor and autonomic impairment that is ultimately fatal. Pathogenic mutations in the transthyretin (TTR) protein lead to destabilization of its tetrameric structure and subsequent formation of amyloid aggregates. Tafamidis is a small-molecule inhibitor that binds selectively to TTR in human plasma and kinetically stabilizes the tetrameric structure of both wild-type TTR and a number of different mutants. Clinical trials indicate that tafamidis slows disease progression in patients with TTR-FAP and reduces the burden of disease, demonstrating improvement in small and large nerve fiber function, modified body mass index and lower extremity neurological examination. Tafamidis has been granted marketing authorization by the European Commission for the treatment of TTR-FAP and the U.S. Food and Drug Administration is currently reviewing this drug for the same indication.
Topics: Amyloid Neuropathies, Familial; Animals; Benzoxazoles; Genotype; Humans; Mutation; Neuroprotective Agents; Prealbumin; Randomized Controlled Trials as Topic
PubMed: 22645721
DOI: 10.1358/dot.2012.48.5.1808486