To find safe alternatives with similar efficacy in UPR inhibition as ISRIB, Halliday et al. screened an NINDS library of drugs that largely have FDA approval and are known to be neurologically active; they identified dibenzoylmethane (DBM) and the licensed antidepressant trazodone as compounds able to cross the blood–brain barrier, restore protein synthesis rates, and profoundly improve memory and survival in prion-diseased mice and a murine model of frontotemporal dementia by acting downstream of eIF2α phosphorylation, similar to ISRIB [16]. Here, EIF2A is linked to frontotemporal dementia.