Abstract
Background Formononetin, which is used as neuroprotective medicine, was reported to have benefits for Alzheimer’s disease (AD). However, little is known on how Formononetin exerts these beneficial effects. In this study, we investigated the molecular mechanisms through which Formononetin increased soluble-APPa (sAPPa) secretion and thus was neuroprotective in human-APP Swedish mutation cell cultures (N2a-APP cell). Method and results By using N2a-APP cell cultures combined with hypoxia treatment, we confirmed that chronic treatment with Formononetin could have neuroprotective effects, which was followed by reduced and increased Caspase3 activity and cell viability. Strikingly, our data revealed that the Caspase3-blocking effect of Formononetin was largely mediated by stimulation of a-secretase cleavage of APP, resulting in increased secretion of its soluble form, sAPPa. Moreover, the protective effect of Formononetin was totally inhibited by TAPI-2, an a-secretase complex inhibitor, suggesting the role of the sAPPa pathway in the neuroprotective response to Formononetin. Furthermore, we also revealed that the stimulation effect of Formononetin on a-secretase activity was mainly a result of up-regulating ADAM10 expression at the transcriptional level. Conclusion
Highlights
Formononetin, which is used as neuroprotective medicine, was reported to have benefits for Alzheimer’s disease (AD)
We investigated the molecular mechanisms through which Formononetin increased soluble-APPa secretion and was neuroprotective in human-APP Swedish mutation cell cultures (N2a-APP cell)
By using N2a-APP cell cultures combined with hypoxia treatment, we confirmed that chronic treatment with Formononetin could have neuroprotective effects, which was followed by reduced and increased Caspase3 activity and cell viability
Summary
Formononetin, which is used as neuroprotective medicine, was reported to have benefits for Alzheimer’s disease (AD). Formononetin could increase soluble-APPa secretion by up-regulating ADAM10 level From 2011 International Conference on Molecular Neurodegeneration Shanghai, China.
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