Abstract

Efficacy of Oleuropein Aglycone in the Treatment of Transthyretin-Amyloidosis

Transthyretin (TTR) is an amyloidogenic protein implicated in diseases such as senile systemic amyloidosis (SSA) and familial amyloid polyneuropathy (FAP), both characterized by extracellular deposition of insoluble amyloid fibrils in heart, peripheral nerves and other organs. In particular, fibrils in FAP patients are composed of single-site mutant TTR and among the numerous pathogenic variants Leu55 → Pro55 (L55P) is highly amyloidogenic and forms amyloid fibrils in vitro. TTR fibrils have been considered directly responsible of tissue impairment in FAP and SSA, but the unstable fibril precursors are increasingly considered the main responsible of cell sufferance and tissue impairment in amyloid diseases. The recent introduction in the clinical practice of synthetic TTR-stabilizing molecules that reduce protein aggregation provides the rationale to search natural effective molecules able to interfere with TTR amyloid aggregation by hindering the appearance of toxic species or by favouring the growth of harmless aggregates. We focused our study on the ability of Oleuropein aglycone (OleA), the main phenolic component of the extra virgin olive oil, to inhibit the toxic effects of wtand L55P- TTR amyloid. Our data offer the possibility to validate and optimize the use of OleA as itself or as a starting point to rationally design promising drugs that could enter in a clinical experimental phase.


Author(s):

Manuela Leri and Monica Bucciantini



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