EIF2A and amyotrophic lateral sclerosis: Guanabenz, like salubrinal and sephin-1 in preclinical studies [59], reduces ER stress and protein overload through a mechanism opposite to that of trazodone and ISRIB, as it leads to increased levels of phosphorylated eIF2α; this allows increased chaperone expression, and has proven effective in some murine models of ALS and in the rare hereditary neuropathy CMT1b [58,59,60], underlining the importance of the UPR in these disorders, and highlighting the need to understand the complex mechanisms and outcomes of drugs acting on this pathway.