I recommend the Primary Papers
The exciting paper by Ma et al. contributes to the accumulating evidence that PERK is involved in neurodegeneration and is potentially a therapeutic target (reviewed in (1)). Our group reported previously the activation of the unfolded protein response (UPR) in AD brain, including specific evidence for the activation of the translational PERK pathway. We detected the active form of the kinase and its phosphorylated substrate peIF2α (2,3)). This fits with the study by Ma et al.
Essentially, these authors show that interference in basic homeostatic pathways can be employed to rescue deficits in synaptic plasticity in an APP/PS1 model. The authors are rightfully cautious to translate their findings to potential treatment for human disease, as interference in homeostatic stress pathways may also have a downside.
It will be interesting to find out more mechanistic detail about the effects of PERK deletion on the progression of AD pathology, in particular tau pathology, as this is closely connected with UPR activation in human brain (3,4). Future studies will have to address how...