Melatonin can decrease ER stress, such as the p-IRE1, p-PERK, GRP78/BiP, and CHOP, in the chronic cerebral hypoperfusion of rats, suggesting that melatonin can improve cognitive impairment following the induction of bilateral typical carotid artery occlusion by attenuating AD markers and reducing ER stress [134]. This evidence concerns the gene EIF2AK3 and Alzheimer disease.