Transthyretin (TTR) is a fascinating protein. Its transport properties for thyroxin and Vitamin A, its classic β-barrel structure, stable homo-tetrameric structure in solution and its phylogenetic evolution have all been of great interest to scientific study. Even the lack of pathology in its absence, in TTR gene knockout mice, has been of great interest. Its entire notoriety in the area of human pathology, however, is that it readily forms amyloid fibrils, usually due to single amino acid mutations in its primary structure but in some cases even when there is no gene or amino acid structural alteration. TTR amyloidosis is strictly a human disease and more than 100 TTR mutations having been associated with the disease. A few of the mutations are found in large kindreds worldwide while many mutations have been found in only single individuals or single families. In depth analysis of this autosomal dominant disease with an appreciation of the variations in phenotypes suggests clues which may help rationalize basic physical and chemical studies of TTR with biochemical processes which must be involved in the generation of clinical disease. This chapter discusses the clinical aspects of the disease and tries to use these observations to contemplate the intricacies of pathogenesis.
ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)