Polyphyletic screen defines distinct classes of plant-derived natural products that oppose tauopathy.

ABSTRACT: Alzheimer's disease (AD) is a debilitating neurodegenerative disease hallmarked by the presence of amyloid-β (Aβ) plaques and tau fibrils but with limited treatment options. Here, we describe two plant-derived natural products with distinct mechanisms of action on tau fibril disaggregation and prionogenic seeding. We first characterized the effects of oolonghomobisflavan A (OFA) and oolonghomobisflavan B (OFB) treatments, which alter the transcriptional landscape toward enhanced proteostasis and reverse the shortened lifespan in a Caenorhabditis elegans model expressing pathogenic human tau ("hTau-expressing"), but increase healthspan. Mechanistically, OFA treatment reduced the burden of tau protein aggregation and promoted tau disaggregation in hTau-expressing C. elegans and

SUBMITTER: Shepard CD 

PROVIDER: S-EPMC12623141 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature