Synergistic Neuroprotective Effects of Ergothioneine and Lactoferrin in APP/PS1 Transgenic Mice and Mouse N2a Cells

Ergothioneine and lactoferrin show antioxidant and neuroprotective effects, but their interactive effects and underlying mechanisms on Alzheimer's disease are unclear. This study aims to investigate the synergistic neuroprotective effect for a combination of ergothioneine and lactoferrin and the molecular mechanisms in APP/PS1 transgenic mice and neuroblast N2a cells. In transgenic mice, the combination of ergothioneine and lactoferrin improved cognitive function and alleviated typical Alzheimer's disease's pathological characteristics of Aβ aggregation and tau phosphorylation. In N2a cells, compared with ergothioneine or lactoferrin alone, their combination synergistically increased cell viability by approximately 15% and decreased apoptosis by 5% in flow cytometry. The combination of ergothioneine and lactoferrin showed a more enhanced antioxidant efficacy through Keap1/Nrf2-mediated mechanisms in comparison to ergothioneine or lactoferrin alone. In summary, the combination of ergothioneine and lactoferrin synergistically enhances neuroprotection in APP/PS1 transgenic mice and N2a cells, providing a foundation for the development of functional foods for the prevention and control of Alzheimer's disease.