Endoplasmic reticulum stress in cerebral ischemia

• ER stress is an essential step in cerebral ischemia.
• ER stress response is initiated by activation of PERK, ATF6 and IRE1.
• ER stress-induced apoptosis is mediated by CHOP, caspase-12 and JNK.
• There are links between ER stress and inflammation and mitochondrial dysfunction.
• ER stress may be used as a therapeutic target for ischemic stroke.

The endoplasmic reticulum (ER) stress is an essential step in the progression of brain ischemia/reperfusion (I/R) injury. It is possible that the timing of events for ER stress signaling regulation is important for the balance of life and death such that ER stress is initially protective, aiming to restore ER homeostasis, whereas prolonged periods of ER stress can be deleterious and damaging. Nevertheless, modulation of ER stress exerts a remarkable protective effect on the ischemic brain and offers the prospect of new stroke therapies. As ER stress is not devoid of deleterious side effects, a better understanding of the reciprocal interaction between the ER and the ischemic brain is essential to harness the full therapeutic potential of ischemic stroke.