Research articleFormononetin attenuates Aβ25-35-induced cytotoxicity in HT22 cells via PI3K/Akt signaling and non-amyloidogenic cleavage of APP

- To the best of our knowledge, this is the first report to demonstrate that Formononetin (Form) alleviated Aβ25-35-induced cytotoxicity in HT22 cells.
- Form promoted non-amyloidogenic cleavage of APP, which might be mediated through ERα-induced PI3K/Akt signaling.
- The protective effects of Form might be associated with the regulation of PI3K/Akt signaling and apoptosis-related proteins cleaved caspase-3 and Bcl-2.

Amyloid beta (Aβ) is the main component of the amyloid plaques that accumulate in the brains of Alzheimer patients. Here, we reported the protective role of Formononetin (Form) against Aβ25-35-induced neurotoxicity in HT22 cells. We found that Form significantly increased the viability of HT22 cells but decreased the cell apoptosis when challenging with Aβ25-35. The inhibitory effects of Form were associated with PI3K/Akt signaling pathway as PI3K inhibitor (LY294002) or ERα specific inhibitor (MPP) blocked the effects. Form also accelerated the non-amyloidogenic process of amyloid precursor protein (APP) by enhancing α-secretase activity and sAPPα release. Altogether, our findings may provide a novel therapeutic target to treat AD sufferers.