APP and Alzheimer disease: Some investigators suggested a mechanism that involves the restoration of neuronal hyperexcitability in AD mice [42,55,56,57], some suggest that blocking RyanR-mediated Ca2+ leakage may lead to decreased endoplasmic reticulum (ER) stress [58], some focused on the role of RyanR-mediated Ca2+ changes in synaptic functions [54], and some suggested dantrolene can decrease β- and γ-secretase activities and APP phosphorylation by affecting Cdk5 and GSk3β kinase activities [45].