The sigma-1 receptor agonist PRE084 has been shown to protect against neuronal damage in stroke via multiple mechanisms; sigma-1 receptor activation regulates brain-derived neurotrophic factors through the NR2A-CaMKIV-TORC1 pathway [20,32], prevents stress-mediated ER apoptosis [21], and protects the BBB [19] in the bilateral common-carotid-artery occlusion-induced global ischemia-reperfusion model. The gene discussed is CRTC1; the disease is Stroke.