Glycosidic scaffold bearing multiple galloyl moieties from pomegranate disrupts transthyretin amyloids.

ABSTRACT: Transthyretin (TTR) amyloidosis involves TTR misfolding and aggregation, causing systemic organ dysfunction. Current therapies stabilize TTR tetramers or reduce TTR production but are less effective against existing amyloid deposits. Here, we identified 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), derived from pomegranate (Punica granatum L.) leaf-and-branch extracts (PGL), as a disruptor of preformed TTR amyloid fibrils. PGG disaggregated fibrils formed by V30M and wild-type (WT) TTR, which are linked to hereditary Transthyretin Amyloidosis (ATTR) (ATTRv) and ATTRwt, respectively. Structure-activity relationship studies showed galloyl moieties are essential. In Caenorhabditis elegans-expressing human TTR_81-127, PGG reduced TTR aggregation and extended both

SUBMITTER: Kagami A 

PROVIDER: S-EPMC12765163 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature