RNA and chondroitin sulfate—BACE1 inhibitory components in protease-digested whitebait (Shirasu): Potential for Alzheimer's disease prevention in mice

The incidence of Alzheimer's disease (AD) is increasing globally, and because no curative treatments exist, prevention is essential. We previously found that food-derived protease-digested whitebait (WPD) inhibits β-secretase (BACE1), which drives amyloid-β production, although the responsible components were unknown. Herein, we identified two WPD fractions, F4B and L1D, with BACE1 inhibitory activity. In AD model mice, F4B significantly suppressed amyloid-β accumulation in the cerebral cortex, whereas L1D tended to suppress accumulation ( p = 0.16). Both fractions reduced glial fibrillary acidic protein expression, indicating in vivo efficacy. F4B absorbed ultraviolet light and lost activity after RNase treatment. The IC 50 value of RNA extracted from F4B was comparable with that of the pre-extracted sample. L1D exhibited no ultraviolet absorption, and its activity was lost after chondroitin sulfate-specific degradation, confirming chondroitin sulfate as its active component. These findings indicate that RNA and chondroitin sulfate in WPD act as BACE1 inhibitors with potential for AD prevention.