PPP1R15A and amyotrophic lateral sclerosis: Guanabenz, an old alpha-2-adrenergic receptor agonist used as an antihypertensive drug, has been shown to modulate the transcription factor-dependent synthesis of PPP1R15A and to reduce the activity of the eIF2α phosphatase complex, resulting in increased levels of phosphorylated eIF2α and reduced ER overload both in vitro cell cultures (22) and in vivo studies in C. elegans and Dario rerio ALS models (23).