ABSTRACT Amyloid‐β‐42 (Aβ42) internalization plays a critical role in Alzheimer's disease (AD) pathology. We investigated whether biflavonoids, natural small molecules, could inhibit Aβ42 uptake and mitigate its cytotoxicity. Biochemical and imaging analyses revealed that biflavonoids dose‐dependently blocked Aβ42 internalization, preventing lamin fragmentation and caspase activation which are considered as key steps in Aβ42‐induced cell death. Confocal microscopy and Western blotting confirmed reduced Aβ42 entry, while aggregation assays in cell‐free conditions demonstrated biflavonoids suppress Aβ42 fibril, oligomer, and β‐sheet formation. These findings suggest biflavonoids exert cytoprotective effects by inhibiting both Aβ42 conformational changes and cellular uptake, positioning them as promising anti‐amyloidogenic agents for AD therapy.
Haque et al. (Thu,) studied this question.