Nitro-oxidative stress and lowered antioxidant defences play a key role in neuropsychiatric disorders such as major depression, bipolar disorder and schizophrenia. The first part of this paper details mitochondrial antioxidant mechanisms and their importance in reactive oxygen species (ROS) detoxification, including details of NO networks, the roles of H₂O₂ and the thioredoxin/peroxiredoxin system, and the relationship between mitochondrial respiration and NADPH production. The second part highlights and identifies the causes of the multiple pathological sequelae arising from self-amplifying increases in mitochondrial ROS production and bioenergetic failure. Particular attention is paid to NAD⁺ depletion as a core cause of pathology; detrimental effects of raised ROS and reactive nitrogen species on ATP and NADPH generation; detrimental effects of oxidative and nitrosative stress on the glutathione and thioredoxin systems; and the NAD⁺-induced signalling cascade, including the roles of SIRT1, SIRT3, PGC-1α, the FOXO family of transcription factors, Nrf1 and Nrf2. The third part discusses proposed therapeutic interventions aimed at mitigating such pathology, including the use of the NAD⁺ precursors nicotinamide mononucleotide and nicotinamide riboside, both of which rapidly elevate levels of NAD⁺ in the brain and periphery following oral administration; coenzyme Q₁₀ which, when given with the aim of improving mitochondrial function and reducing nitro-oxidative stress in the brain, may be administered via the use of mitoquinone, which is in essence ubiquinone with an attached triphenylphosphonium cation; and N-acetylcysteine, which is associated with improved mitochondrial function in the brain and produces significant decreases in oxidative and nitrosative stress in a dose-dependent manner.

氮氧化应激和抗氧化防御能力的降低在神经精神疾病如重度抑郁，躁郁症和精神分裂症中起关键作用。本文的第一部分详细介绍了线粒体的抗氧化机理及其在活性氧（ROS）排毒中的重要性，包括NO网络的详细信息，H ₂ O ₂和硫氧还蛋白/过氧化物酶系统的作用以及线粒体呼吸与NADPH的关系。生产。第二部分突出并确定了线粒体ROS产生的自扩增增加和生物能衰竭导致的多个病理后遗症的原因。特别注意NAD ⁺枯竭是病理的核心原因；活性氧和活性氮增加对ATP和NADPH产生的不利影响；氧化和亚硝化应激对谷胱甘肽和硫氧还蛋白系统的有害影响；NAD ⁺诱导的信号级联反应，包括SIRT1，SIRT3，PGC-1α，FOXO转录因子家族，Nrf1和Nrf2的作用。第三部分讨论了拟议的旨在减轻这种病理状况的治疗性干预措施，包括使用NAD ⁺前体烟酰胺单核苷酸和烟酰胺核糖苷，它们在口服后都会迅速提高大脑和周围NAD ^+的水平；辅酶Q ₁₀当目的是改善线粒体功能并减少脑中的硝基氧化应激时，可通过使用米托醌（本质上是泛醌与三苯基phosph阳离子相连）来给药；和Ñ乙酰半胱氨酸，其与改善线粒体功能在大脑相关联并产生氧化和亚硝化应激显著降低以剂量依赖的方式。