Protective Effects of Erinacine A against Neuro 2a Cell Death Induced by Endoplasmic Reticulum Stress and Amyloid-Beta Aggregates

Amyloid-beta (Aβ) aggregation is a characteristic feature of Alzheimer’s disease (AD). Aβ has been reported to cause neurodegeneration and to induce endoplasmic reticulum (ER) stress. Erinacine A may inhibit mild dementia progression. However, their direct neuroprotective effects have not been reported. Here, we analyzed the effects of erinacine A on ER stress-induced apoptosis in mouse neuroblastoma Neuro2a cells. Erinacine A exhibited significant protection against both Aβ aggregation and ER stress. It inhibited caspase activation in Neuro2a cells and prevented further caspase activation. Moreover, it prevented neuronal cell death by inhibiting ER stress-induced apoptotic signaling. Assessment of the direct effect of erinacine A on Aβ aggregation revealed that it significantly reduced the level of Aβ 1–40 aggregation. This is the first study to demonstrate the direct protective effects of erinacine A on neuronal cells through multiple mechanisms. Erinacine A can be used to prevent or slow AD progression.