Reactive oxygen and nitrogen species: Weapons of neuronal destruction

Recent advancements in understanding the biochemical actions of reactive oxygen and nitrogen species (RONS) have identified many biological targets that reliably serve as indices of oxidative and nitrative stress. Oxidative stress occurs when uncontrolled and excessive amounts of oxidants are produced, resulting in the formation of oxidized macromolecules, whereas nitrative stress occurs when excessive reactive nitrogen species are produced resulting in the formation of nitrated macromolecules. The most frequently detected oxidant-modified biological targets include: 1) the polyunsaturated fatty acid oxidation products, isoprostanes and the electrophiles 4-hydroxy-2(E)nonenal (4-HNE) and malondialdehyde (MDA), 2) 8-hydroxy-2′-deoxyguanosine, the most studied product of DNA oxidation, and 3) oxidatively modified proteins including advanced glycation endproducts (AGEs) and proteins with reactive carbonyl side groups. Modification by reactive nitrogen species (reactive species derived from nitric oxide (NO) or metabolites of NO such as dinitrogen trioxide, nitrous acid, nitrogen dioxide, and peroxynitrite) lead to the formation of nitrated macromolecules by the addition of a nitro(-NO2) group. Biological targets modified by nitration include: 1) tyrosine and tryptophan residues in proteins, 2) polyunsaturated fatty acids, 3) DNA bases, and 4) sugars. All of these oxidative modifications can be readily detected in biological samples, providing molecular footprints to track the generation and actions of RONS. Moreover, the identification and quantification of these biomarkers may provide a reliable assessment of disease risk and severity.