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- Title
Orally administered diflunisal stabilizes transthyretin against dissociation required for amyloidogenesis.
- Authors
Sekijima, Yoshiki; Dendle, Maria A; Kelly, Jeffery W
- Abstract
Rate-limiting transthyretin (TTR) tetramer dissociation and monomer misfolding enable misassembly into numerous aggregate morphologies including amyloid, a process genetically linked to and thought to cause amyloid pathology. T119M TTR trans-suppressor subunit inclusion into tetramers otherwise composed of disease-associated subunits ameliorates human amyloidosis by increasing the tetramer dissociation barrier. Diflunisal binding to the 99% unoccupied L-thyroxine binding sites in TTR also increases the tetramer dissociation barrier; hence, we investigated the feasibility of using diflunisal for the treatment of human TTR amyloidosis using healthy volunteers.
- Publication
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, 2006, Vol 13, Issue 4, p236
- ISSN
1350-6129
- Publication type
Journal Article
- DOI
10.1080/13506120600960882