There is a strong interest in transthyretin (TTR) in connection with protein evolution, medical and clinical research. Thus, this is an exciting time for experts in TTR research to come together to write a monograph covering both the basic and the clinical research into TTR.
Transthyretin is a protein found in human blood and cerebrospinal fluid. It is directly involved in the transport of thyroid hormones, and indirectly in that of retinol. These hormones are essential for normal growth and development, particularly that of the brain. Spontaneous and inherited diseases affecting transthyretin result in amyloidosis. More than 80 point mutations in transthyretin lead to a variety of illnesses. Liver transplants are the most common treatment, although much research is also being carried out in drug therapies.
The evolution of transthyretin has been extensively investigated - from humans to bacteria, invertebrate animals and plants. The structure of the protein has not changed, but its function has changed significantly. This is a most exciting example for the study of the evolution of protein structure-function relationships.
This monograph will bring the reader up to date on the latest developments and discoveries.
Zusammenfassung
Since its ?rst description in 1942 in both serum and cerebrospinal ?uid, transthyretin (TTR) has had an eventful history, including changes in name from prealbumin to thyroxine-binding prealbumin to transthyretin as knowledge increased about its functions. TTR is synthesised in a wide range of tissues in humans and other eutherian mammals: the liver, choroid plexus (blood- cerebrospinal ?uid barrier), retinal pigment epithelium of the eye, pancreas, intestine and meninges. However, its sites of synthesis are more restricted in other vertebrates. This implies that the number of tissues synthesising TTR during vertebrate evolution has increased, and raises questions about the selection pressures governing TTR synthesis. TTR is most widely known as a distributor of thyroid hormones. In addition, TTR binds retinol-binding protein, which binds retinol. In this way, TTR is also involved with retinoid distribution. More recently, TTR has been demonstrated to bind a wide variety of endocrine disruptors including drugs, pollutants, industrial compounds, heavy metals, and some naturally occurring plant ?avonoids. These not only interfere with thyroid hormone delivery in the body, but also transport such endocrine disruptors into the brain, where they have the potential to accumulate.
Inhalt
Mechanisms of Molecular Recognition: Structural Characteristics of Transthyretin Ligand Interactions.- Transthyretin Synthesis During Development and Evolution: What the Marsupials Revealed.- Evolution of Transthyretin Gene Structure.- Evolutionary Insights from Fish Transthyretin.- The Salmonella sp. TLP: A Periplasmic 5-Hydroxyisourate Hydrolase.- Vertebrate 5-Hydroxyisourate Hydrolase Identification, Function, Structure, and Evolutionary Relationship with Transthyretin.- Transthyretin-Related and Transthyretin-like Proteins.- The TransthyretinRetinol-Binding Protein Complex.- Transthyretin and Retinol-Binding Protein: Implications in Fish Physiology.- Transthyretin and Endocrine Disruptors.- Genetics: Clinical Implications of Transthyretin Amyloidosis.- Molecular Pathogenesis Associated with Familial Amyloidotic Polyneuropathy.- Histidine 31: The Achilles' Heel of Human Transthyretin. Microheterogeneity is Not Enough to Understand the Molecular Causes of Amyloidogenicity.- New Therapeutic Approaches for Familial Amyloidotic Polyneuropathy (FAP).- Liver Transplantation for Transthyretin Amyloidosis.- Mouse Models of Transthyretin Amyloidosis.- What Have We Learned from Transthyretin-Null Mice: Novel Functions for Transthyretin?.- Transthyretin Null Mice: Developmental Phenotypes.- Transthyretin Null Mice as a Model to Study the Involvement of Transthyretin in Neurobiology: From Neuropeptide Processing to Nerve Regeneration.- Plasma Transthyretin Reflects the Fluctuations of Lean Body Mass in Health and Disease.- Erratum to.