The UPR and the Anti-oxidant Response: Relevance to Sleep and Sleep Loss

Oxidative stress has been linked to various physiological and pathological processes such as aging and neurological disorders. Recent evidence has now implicated a role for oxidative stress in sleep and sleep loss. Studies suggest that wakefulness results in an oxidative burden and sleep provides a protective mechanism against these harmful effects. Prolonged wakefulness/sleep deprivation activates an adaptive stress pathway termed the unfolded protein response (UPR), which temporarily guards against the deleterious consequences of reactive oxygen species. The UPR affects the function of the endoplasmic reticulum, which is the site for integral and secretory membrane processing and folding. Several downstream effectors of the UPR operate in an antioxidant capacity to reduce the load of these toxic species; a process that may be important in delaying the progression of neurodegenerative diseases. This review will highlight the molecular components of the UPR that ameliorate the accumulation of oxidative stress and may therefore provide potential therapeutic targets.