Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor encoded by NFE2L2. Under oxidative stress, Nrf2 does not undergo its normal cytoplasmic degradation but instead travels to the nucleus, where it binds to a DNA promoter and initiates transcription of anti-oxidative genes. Nrf2 upregulation is associated with increased cellular levels of glutathione disulfide, glutathione peroxidase, glutathione transferases, thioredoxin and thioredoxin reductase. Given its key role in governing the cellular antioxidant response, upregulation of Nrf2 has been suggested as a common therapeutic target in neuropsychiatric illnesses such as major depressive disorder, bipolar disorder and schizophrenia, which are associated with chronic oxidative and nitrosative stress, characterised by elevated levels of reactive oxygen species, nitric oxide and peroxynitrite. These processes lead to extensive lipid peroxidation, protein oxidation and carbonylation, and oxidative damage to nuclear and mitochondrial DNA. Intake of N-acetylcysteine, coenzyme Q₁₀ and melatonin is accompanied by increased Nrf2 activity. N-acetylcysteine intake is associated with improved cerebral mitochondrial function, decreased central oxidative and nitrosative stress, reduced neuroinflammation, alleviation of endoplasmic reticular stress and suppression of the unfolded protein response. Coenzyme Q₁₀, which acts as a superoxide scavenger in neuroglial mitochondria, instigates mitohormesis, ameliorates lipid peroxidation in the inner mitochondrial membrane, activates uncoupling proteins, promotes mitochondrial biogenesis and has positive effects on the plasma membrane redox system. Melatonin, which scavenges mitochondrial free radicals, inhibits mitochondrial nitric oxide synthase, restores mitochondrial calcium homeostasis, deacetylates and activates mitochondrial SIRT3, ameliorates increased permeability of the blood-brain barrier and intestine and counters neuroinflammation and glutamate excitotoxicity.

核因子红细胞 2 相关因子 2 (Nrf2) 是由NFE2L2编码的转录因子. 在氧化应激下，Nrf2 不会进行正常的细胞质降解，而是进入细胞核，在那里它与 DNA 启动子结合并启动抗氧化基因的转录。Nrf2 上调与谷胱甘肽二硫化物、谷胱甘肽过氧化物酶、谷胱甘肽转移酶、硫氧还蛋白和硫氧还蛋白还原酶的细胞水平增加有关。鉴于其在控制细胞抗氧化反应中的关键作用，Nrf2 的上调已被认为是神经精神疾病（如重度抑郁症、双相情感障碍和精神分裂症）的常见治疗靶点，这些疾病与慢性氧化和亚硝化应激相关，其特征是水平升高活性氧、一氧化氮和过氧亚硝酸盐。这些过程导致广泛的脂质过氧化，蛋白质氧化和羰基化，以及对核和线粒体 DNA 的氧化损伤。摄入量N-乙酰半胱氨酸、辅酶 Q ₁₀和褪黑激素伴随着 Nrf2 活性的增加。N-乙酰半胱氨酸的摄入与改善脑线粒体功能、减少中枢氧化和亚硝化应激、减少神经炎症、缓解内质网应激和抑制未折叠蛋白反应有关。辅酶 Q ₁₀，在神经胶质线粒体中作为超氧化物清除剂，引发线粒体激素，改善线粒体内膜中的脂质过氧化，激活解偶联蛋白，促进线粒体生物发生并对质膜氧化还原系统具有积极作用。褪黑激素可清除线粒体自由基、抑制线粒体一氧化氮合酶、恢复线粒体钙稳态、去乙酰化并激活线粒体 SIRT3、改善血脑屏障和肠道通透性增加并对抗神经炎症和谷氨酸兴奋性毒性。