Accordingly, dantrolene, a negative allosteric modulator of RyR—and its central nervous system (CNS)-penetrant version Ryanodex—has been shown to reduce amyloid pathology, normalize ER Ca2+ homeostasis, restore synaptic structure and density, normalize synaptic plasticity, and improve behavioral performance in mouse models of AD [101,109,110]. This evidence concerns the gene RYR2 and Alzheimer disease.