Neuroprotection against beta-amyloid toxicity by the novel estrogen receptor modulator STX requires convergent signaling pathways

In combination with our previous studies, these results indicate that engagement of GqMER by STX promotes neuroprotective responses via convergent signaling pathways that mitigate the effects of Aβ toxicity on mitochondrial function, synaptic integrity, and neuronal calcium (Ca²⁺) homeostasis. They also provide the framework for testing the mechanisms of STX neuroprotection <i>in vivo</i>, using mouse AD models. Since STX has been shown to provide many of the beneficial effects of 17β-estradiol in the brain without its adverse side effects (including feminizing effects in males), these results support the hypothesis that STX might have therapeutic potential in patients at risk of AD.