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Role of Nitric Oxide Signaling Pathways in Brain Injuries

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Nitric oxide (NO) is involved in many physiological and pathological brain processes. NO is probably the smallest and most versatile bioactive molecule identified. NO signaling in excitable tissues requires rapid and controlled delivery of NO to specific cellular targets. This tight control of NO signaling is largely regulated at the level of its biosynthesis. NO production might lead either to toxicity or to neuroprotection depending on the level of NO, the location of NO production, the extent of oxidative stress and the type of neurodegenerative process. It has been suggested that NO directly acts as an antioxidant. This protective effect is mediated by small fluxes of NO (<1 μmol/L). This is consistent with the fact that NO terminates lipid peroxidation reactions and suggests that the production of NO is a major protective mechanism against oxidative stress in vivo. In fact it has been demonstrated, in vitro as well as in vivo, that during brain insult NO might be part of the physiological response to injury. In general, it is accepted that a normal pathophysiologic response of the damaged tissue may involve controlled NO production and the inhibition of this response may interfere with the normal repair process. Nevertheless, it has been suggested that a high production of NO after the induction of iNOS expression can interact with superoxide anion generated by the mitochondria or by other mechanisms, leading to the formation of the potent oxidant species peroxynitrite. These events would result in cell damage and altered neuronal physiological function. The present review focuses on the role of NO as an important neuromodulator that can exert both neurotoxic and neuroprotective effects in different injuries.

Keywords: Brain injuries; chronic stress; intracellular signaling; neuroprotection; neurotoxicity; nitric oxide

Document Type: Research Article

Publication date: September 1, 2010

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  • Current Chemical Biology aims to publish full-length and mini reviews on exciting new developments at the chemistry-biology interface, covering topics relating to Chemical Synthesis, Science at Chemistry-Biology Interface and Chemical Mechanisms of Biological Systems.

    Current Chemical Biology covers the following areas: Chemical Synthesis (Syntheses of biologically important macromolecules including proteins, polypeptides, oligonucleotides, oligosaccharides etc.; Asymmetric synthesis; Combinatorial synthesis; Diversity-oriented synthesis; Template-directed synthesis; Biomimetic synthesis; Solid phase biomolecular synthesis; Synthesis of small biomolecules: amino acids, peptides, lipids, carbohydrates and nucleosides; and Natural product synthesis).

    Science at Chemistry-Biology Interface (Chemical informatics; Macromolecular catalysts and receptors; Enzymatic synthesis; Biosynthetic engineering; Combinatorial biosynthesis; Plant cell based chemistry; Bacterial and viral cell based chemistry; Chemistry of cellular processes in plants/animals; Receptor chemistry; Cell signaling chemistry; Drug design through understanding of disease processes; Synthetic biology; New high throughput screening techniques; Small molecular array fabrication; Chemical genomics; Chemical and biological approaches to carbohydrates proteins and nucleic acids design; Chemical and biological regulation of biosynthetic pathways; and Unnatural biomolecular analogs).

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