Targeting the kinase insert loop of PERK selectively modulates PERK signaling without systemic toxicity in mice
The unfolded protein response (UPR) is critical for proteostasis in all tissues. However, chronic UPR activity in protein aggregation–associated neurodegenerative diseases detrimentally suppresses protein synthesis that is necessary for neuronal function and survival, as well as for cognition. Hughes et al. found that the phosphorylation of a threonine residue in the stress response kinase PERK…
