Hypomorphic PERK promotes a maladaptive phenotype in response to pathologic tau

A major challenge in the field of tauopathies, such as progressive supranuclear palsy (PSP) is identification of effective therapeutic targets. PKR‐like endoplasmic reticulum (ER) kinase haplotype A (PERK‐A) adapts cells undergoing ER stress. PERK haplotype B (PERK‐B) does not resolve ER stress effectively and increases the risk for PSP. The mechanism by which PERK‐A and ‐B confer distinct outcomes remains unknown. The overall hypothesis is that PERK‐B promotes maladaptive response that increases tauopathy outcomes.