EIF2A and Parkinson disease: However, prolonged and/or excessive ER stress leads to neuronal death.52 In the brain of PD patients, expression of UPR activation markers, phospho-PERK and phospho-eIF2α, was observed to be increased and colocalized with α-Syn.53 An in vivo study further showed that toxic α-Syn oligomers accumulate within ER lumen and α-Syn oligomer-dependent ER stress can be rescued by treatment with Salubrinal, which inhibits eIF2α and thus decreases protein overload54,55.