Abstract
Transthyretin (TTR) amyloidogenesis involves the formation, aggregation, and deposition of amyloid fibrils from tetrameric TTR in different organs and tissues. While the result of amyloidoses is the accumulation of amyloid fibrils resulting in end-organ damage, the nature, and sequence of the molecular causes leading to amyloidosis may differ between the different variants. In addition, fibril accumulation and toxicity vary between different mutations. Structural changes in amyloidogenic TTR have been difficult to identify through X-ray crystallography; but nuclear magnetic resonance spectroscopy has revealed different chemical shifts in the backbone structure of mutated and wild-type TTR, resulting in diverse responses to the cellular conditions or proteolytic stress. Toxic mechanisms of TTR amyloidosis have different effects on different tissues. Therapeutic approaches have evolved from orthotopic liver transplants to novel disease-modifying therapies that stabilize TTR tetramers and gene-silencing agents like small interfering RNA and antisense oligonucleotide therapies. The underlying molecular mechanisms of the different TTR variants could be responsible for the tropisms to specific organs, the age at onset, treatment responses, or disparities in the prognosis.
Highlights
Transthyretin (TTR) is a protein produced in the liver and choroid plexus that carries thyroxine and holo-retinol binding protein in serum [1,2]
ATTR amyloidosis is caused by the deposition of insoluble amyloid fibrils in extracellular tissues of most organs, including the ones that may not display signs of disease [3]
While the result of amyloidoses is the accumulation of amyloid fibrils resulting in endorgan damage, the nature, and sequence of the molecular causes leading to amyloidosis may differ between the different variants [8]
Summary
Transthyretin (TTR) is a protein produced in the liver and choroid plexus that carries thyroxine and holo-retinol binding protein in serum [1,2]. ATTR amyloidosis is caused by the deposition of insoluble amyloid fibrils in extracellular tissues of most organs, including the ones that may not display signs of disease [3]. As new disease-modifying therapies emerge, a complete understanding of the molecular mechanisms subserving the development of TTR amyloidosis will provide helpful insights into the heterogenic manifestations of this misfolding disease. This knowledge could aid in designing new therapeutic strategies and drugs or implementing tailored approaches for specific subpopulations of patients suffering from TTR amyloidosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
