IDENTIFICATION OF NEW DIFLUNISAL DERIVATIVES AS POTENT IN W77?O TRANSTHYRETIN FIBRIL INHIBITORS

摘要

Fibril formation and accumulation in peripheral organs is a common feature of both senile systemic amyloidosis (SSA) and familial amyloid polyneuropathy (FAP). The causative agent of such fibrils appears to be the protein transthyretin (TTR). Under physiological conditions, TTR is a stable tetramer, therefore, unit dissociation and subsequent conformational changes of the monomers are necessary events in producing TTR fibrils. In accordance to this hypothesis, therapeutic strategies for FAP and SSA have focused in finding molecules that could bind to TTR and stabilize its tetrameric form (1).