Nitro-oxidative stress (NOS) plays a fundamental role in aging, as well as in the pathogenesis of neurodegenerative disorders, and major depression (MD). The latter is a very frequent psychiatric illness characterized by accelerated aging, neurodegeneration, high comorbidity with age-related disorders, and premature mortality; all of these conditions find an explanation in an altered redox homeostasis. If aging, neurodegeneration, and major depression share a common biological base in their pathophysiology, common therapeutic tools could be investigated for the prevention and treatment of these disorders. As an example, antidepressants have been demonstrated to present neuroprotective and anti-inflammatory properties and to stimulate neurogenesis. In parallel, antioxidants that stimulate the antioxidant defense systems and interact with the monoaminergic system show an antidepressant-like activity. Further research on this topic could lead, in the near future, to the expansion of the therapeutic possibilities for the treatment of NOS-related disorders. 1. Nitro-Oxidative Stress Reactive oxygen/nitrogen species (ROS/RNS) are by-products of cellular metabolism, primarily generated from mitochondria [1]. More specifically, ROS are reactive molecules derived from oxygen that can be free radicals (superoxide), hydroxyl radical (the most reactive and potentially cytotoxic species), or nonradicals (hydrogen peroxide). They can also be classified as ions (superoxide) and nonions (hydrogen peroxide). RNS, instead, are reactive species derived from nitrogen that can be classified as ions (peroxynitrite) or nonions (nitric oxide). ROS and RNS are involved in many physiological processes, such as cellular response to stress, modulation of autophagy, mitochondrial network, signaling, and apoptosis [2, 3]. However, being highly reactive species, they can lead to nitro-oxidative damage of proteins, lipids, DNA, and sugars, thus negatively affecting the cellular functioning [4, 5]. The potentially deleterious effects of ROS and RNS are neutralized by the endogenous antioxidative defense systems that include nonenzymatic and enzymatic antioxidants, such as glutathione, vitamin C, flavonoids, bilirubin, superoxide dismutase, catalases, and glutathione peroxidase [6, 7]. In addition, certain compounds are termed “upstream antioxidants,” since they prevent the formation of ROS/RNS (e.g., anti-inflammatory drugs, calcium antagonists). When the redox homeostasis (balance between oxidants-nitrosants production and elimination) fails, thus resulting in a preponderance of
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