Investigators have suggested that melatonin as a neuroprotectant in cerebral ischemia may involve mechanisms like reduction in ROS production, and activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2), which is a master regulator of endogenous antioxidant defenses followed by overexpression of phase II enzymes such as heme oxygenase-1, which has a potent antioxidant and anti-inflammatory effect [131]. Here, NFE2L2 is linked to brain ischemia.