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Nobiletin, isolated from citrus peels, improved the memory in memory-impaired animals and further that Aβ levels and depositions were markedly decreased in their brains, and that evoked CREB-dependent transcription via activating PKAJERKICREB signaling pathway. Recently, we demonstrated that nobiletin increases the expression of several genes relating to memory formation, transcription and Aβ degradation. Remarkably, nobiletin significantly up-regulated the expression of neprilysin gene, which plays a major role in Aβ degradation. However, the mechanism of action of nobiletin on Aβ degradation under AD pathological conditions is still inknown. To clarify this problem, we examined whether nobiletin could enhance the reduction in intra- and extracellular Aβ using human iPS cell-derived AD model neurons. Our results show that the intra- and extracellular Aβ were decreased by nobiletin in the AD model neurons. In conclusion, since it is possible to attenuate Aβ-induced toxicity in neurons by nobiletin, our findings suggest that nobiletin could be a novel functional food or seed drug for the prevention of AD. [ABSTRACT FROM AUTHOR]