Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity(698 views) Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Stella AM
Department of Chemistry, Biochemistry and Molecular Biology Section, Faculty of Medicine, University of Catania, Catania, Italy. calabres@unict.it
Institute of Pharmacology, Catholic University School of Medicine, Roma, Italy
Department of Internal Medicine, Catholic University School of Medicine, Roma, Italy
References: Guix, F. X., Uribesalgo, I., Coma, M. & Munoz, F. J. The physiology and pathophysiology of nitric oxide in the brain. Prog. Neurobiol. 76, 126-152 (2005). A comprehensive review of NO functions in the brainRivier, C. Role of gaseous neurotransmitters in the hypothalamic- pituitary-adrenal axis. Ann. NY Acad. Sci. 933, 254-264 (2001). A useful paper for understanding the controversial action of NO in the regulation of the stress axisMcCann, S.M., The nitric oxide hypothesis of brain aging (1997) Exp. Gerontol, 32, pp. 431-44
Toda, N., Ayajiki, K., Okamura, T., Nitric oxide and penile erectile function (2005) Pharmacol. Ther, 106, pp. 233-266
Takahashi, T., Pathophysiological significance of neuronal nitric oxide synthase in the gastrointestinal tract (2003) J. Gastroenterol, 38, pp. 421-430
Currò, D., Preziosi, P., Non-adrenergic noncholinergic relaxation of the rat stomach (1998) Gen. Pharmacol, 31, pp. 697-703
Pacher, P., Beckman, J.S., Liaudet, L., Nitric oxide and peroxynitrite in health and disease (2007) Physiol. Rev, 87, pp. 315-424
Hirst, D.G., Robson, T., Nitrosative stress in cancer therapy (2007) Front. Biosci, 12, pp. 3406-3418
Ridnour, L.A., The chemistry of nitrosative stress induced by nitric oxide and reactive nitrogen oxide species. Putting perspective on stressful biological situations (2004) Biol. Chem, 385, pp. 1-10
Sultana, R., Identification of nitrated proteins in Alzheimer's disease brain using a redox proteomics approach (2006) Neurobiol. Dis, 22, pp. 76-87
Castegna A. et al. Proteomic identification of nitrated proteins in Alzheimer's disease brain. J. Neurochem. 85, 1394-1401 (2003). This was the first proteomics study to identify nitrated proteins in the brain of patients with Alzheimer's diseaseBredt, D.S., Endogenous nitric oxide synthesis: Biological functions and pathophysiology (1999) Free Radic. Res, 31, pp. 577-596
Dawson, T. M. & Snyder, S. H. Gases as biological messengers: nitric oxide and carbon monoxide in the brain. J. Neurosci. 14, 5147-5159 (1994). This paper provides details on the distribution of nNOS in the CNS and PNSRodrigo, J., Localization of nitric oxide synthase in the adult rat brain (1994) Philos. Trans. R. Soc. Lond. B Biol. Sci, 345, pp. 175-221
Vincent, S.R., Kimura, H., Histochemical mapping of nitric oxide synthase in the rat brain (1992) Neuroscience, 46, pp. 755-784
Bredt, D.S., Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase (1991) Neuron, 7, pp. 615-624
De Giorgio, R., Nitric oxide producing neurons in the monkey and human digestive system (1994) J. Comp. Neurol, 342, pp. 619-627
Magee, T., Cloning of a novel neuronal nitric oxide synthase expressed in penis and lower urinary tract (1996) Biochem. Biophys. Res. Commun, 226, pp. 145-151
Calabrese, V., Butterfield, D.A., Scapagnini, G., Stella, A.M., Maines, M.D., Redox regulation of heat shock protein expression by signaling involving nitric oxide and carbon monoxide: Relevance to brain aging, neurodegenerative disorders, and longevity (2006) Antioxid. Redox Signal, 8, pp. 444-477
Colasanti, M., Expression of a NOS-III-like protein in human astroglial cell culture (1998) Biochem. Biophys. Res. Commun, 252, pp. 552-555
Rajasekaran, M., Ex vivo expression of nitric oxide synthase isoforms (eNOS/iNOS) and calmodulin in human penile cavernosal cells (1998) J. Urol, 160, pp. 2210-2215
Arnold, W. P., Mittal, C. K., Katsuki, S. & Murad, F. Nitric oxide activates guanylate cyclase and increases guanosine 3?-5?-cyclic monophosphate levels in various tissue preparations. Proc. Natl Acad. Sci. USA 74, 3203-3207 (1977). A milestone paper about the ability of NO to activate sGCKrumenacker, J.S., Hanafy, K.A., Murad, F., Regulation of nitric oxide and soluble guanylyl cyclase (2004) Brain Res. Bull, 62, pp. 505-515
Nakane, M., Soluble guanylyl cyclase: Physiological role as an NO receptor and the potential molecular target for therapeutic application (2003) Clin. Chem. Lab. Med, 41, pp. 865-870
Uretsky, A.D., Weiss, B.L., Yunker, W.K., Chang, J.P., Nitric oxide produced by a novel nitric oxide synthase isoform is necessary for gonadotropin-releasing hormone-induced growth hormone secretion via a cGMP-dependent mechanism (2003) J. Neuroendocrinol, 15, pp. 667-676
Mollace, V., Muscoli, C., Masini, E., Cuzzocrea, S., Salvemini, D., Modulation of prostaglandin biosynthesis by nitric oxide and nitric oxide donors (2005) Pharmacol. Rev, 57, pp. 217-252
Motterlini, R., Green, C.J., Foresti, R., Regulation of heme oxygenase-1 by redox signals involving nitric oxide (2002) Antioxid. Redox Signal, 4, pp. 615-624
Contestabile, A., Ciani, E., Role of nitric oxide in the regulation of neuronal proliferation, survival and differentiation (2004) Neurochem. Int, 45, pp. 903-914
Riccio, A. et al. A nitric oxide signaling pathway controls CREB-mediated gene expression in neurons. Mol. Cell 21, 283-294 (2006). This study demonstrates that the NO pathway controls CREB-DNA binding and CRE-mediated gene expressionFoster, M.W., McMahon, T.J., Stamler, J.S., S-nitrosylation in health and disease (2003) Trends Mol. Med, 9, pp. 160-168
Garthwaite, J., Charles, S. L. & Chess-Williams, R. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature 336, 385-388 (1988). A landmark paper that demonstrates that EDRF, the early name given to NO, is involved in neurotransmissionPalmer, R.M., Ferrige, A.G., Moncada, S., Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor (1987) Nature, 327, pp. 524-526
Ignarro, L. J., Buga, G. M., Wood, K. S., Byrns, R. E. & Chaudhuri, G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc. Natl Acad. Sci. USA 84, 9265-9269 (1987). A milestone paper that reveals the identity of EDRF as NOGarthwaite, J., Boulton, C.L., Nitric oxide signaling in the central nervous system (1995) Annu. Rev. Physiol, 57, pp. 683-706
Sanders, K.M., Ward, S.M., Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission (1992) Am. J. Physiol, 262, pp. G379-G392
Prast, H., Tran, M.H., Fischer, H., Philippu, A., Nitric oxide-induced release of acetylcholine in the nucleus accumbens: Role of cyclic GMP, glutamate, and GABA (1998) J. Neurochem, 71, pp. 266-273
Getting, S.J., Segieth, J., Ahmad, S., Biggs, C.S., Whitton, P.S., Biphasic modulation of GABA release by nitric oxide in the hippocampus of freely moving rats in vivo (1996) Brain Res, 717, pp. 196-199
Ohkuma, S., Katsura, M., Chen, D.Z., Narihara, H., Kuriyama, K., Nitric oxide-evoked [3H]γ-aminobutyric acid release is mediated by two distinct release mechanisms (1996) Brain Res. Mol. Brain Res, 36, pp. 137-144
Lonart, G., Wang, J., Johnson, K.M., Nitric oxide induces neurotransmitter release from hippocampal slices (1992) Eur. J. Pharmacol, 220, pp. 271-272
Lorrain, D.S., Hull, E.M., Nitric oxide increases dopamine and serotonin release in the medial preoptic area (1993) Neuroreport, 5, pp. 87-89
Kaehler, S.T., Singewald, N., Sinner, C., Philippu, A., Nitric oxide modulates the release of serotonin in the rat hypothalamus (1999) Brain Res, 835, pp. 346-349
Bon, C.L., Garthwaite, J., On the role of nitric oxide in hippocampal long-term potentiation (2003) J. Neurosci, 23, pp. 1941-1948
Boulton, C.L., Southam, E., Garthwaite, J., Nitric oxide-dependent long-term potentiation is blocked by a specific inhibitor of soluble guanylyl cyclase (1995) Neuroscience, 69, pp. 699-703
Chien, W.L., Enhancement of long-term potentiation by a potent nitric oxide-guanylyl cyclase activator, 3-(5-hydroxymethyl-2-furyl)-1- benzylindazole (2003) Mol. Pharmacol, 63, pp. 1322-1328
Hars, B., Endogenous nitric oxide in the rat pons promotes sleep (1999) Brain Res, 816, pp. 209-219
Datta, S., Patterson, E.H., Siwek, D.F., Endogenous and exogenous nitric oxide in the pedunculopontine tegmentum induces sleep (1997) Synapse, 27, pp. 69-78
Cavas, M., Navarro, J.F., Effects of selective neuronal nitric oxide synthase inhibition on sleep and wakefulness in the rat (2006) Prog. Neuropsychopharmacol. Biol. Psychiatry, 30, pp. 56-67
Stern, J.E., Nitric oxide and homeostatic control: An intercellular signalling molecule contributing to autonomic and neuroendocrine integration? (2004) Prog. Biophys. Mol. Biol, 84, pp. 197-215
Toni, R., Malaguti, A., Benfenati, F., Martini, L., The human hypothalamus: A morpho-functional perspective (2004) J. Endocrinol. Invest, 27, pp. 73-94
Tsigos, C., Chrousos, G.P., Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress (2002) J. Psychosom. Res, 53, pp. 865-871
Barberis, C., Tribollet, E., Vasopressin and oxytocin receptors in the central nervous system (1996) Crit. Rev. Neurobiol, 10, pp. 119-154
Tringali, G., Aubry, J.M., Navarra, P., Pozzoli, G., Lamotrigine inhibits basal and Na+-stimulated, but not Ca2+-stimulated, release of corticotropin-releasing hormone from the rat hypothalamus (2006) Psychopharmacology (Berl.), 188, pp. 386-392
Costa, A., Trainer, P., Besser, M., Grossman, A., Nitric oxide modulates the release of corticotropin-releasing hormone from the rat hypothalamus in vitro (1993) Brain Res, 605, pp. 187-192
Yasin, S., Nitric oxide modulates the release of vasopressin from rat hypothalamic explants (1993) Endocrinology, 133, pp. 1466-1469
Nguyen, K.T., Exposure to acute stress induces brain interleukin-1β protein in the rat (1998) J. Neurosci, 18, pp. 2239-2246
Karanth, S., Lyson, K., McCann, S.M., Role of nitric oxide in interleukin 2-induced corticotropin-releasing factor release from incubated hypothalami (1993) Proc. Natl Acad. Sci. USA, 90, pp. 3383-3387
Rivier, C., Role of nitric oxide in regulating the rat hypothalamic-pituitary-adrenal axis response to endotoxemia (2003) Ann. NY Acad. Sci, 992, pp. 72-85
Kadekaro, M., Nitric oxide modulation of the hypothalamo-neurohypophyseal system (2004) Braz. J. Med. Biol. Res, 37, pp. 441-450
Brann, D.W., Bhat, G.K., Lamar, C.A., Mahesh, V.B., Gaseous transmitters and neuroendocrine regulation (1997) Neuroendocrinology, 65, pp. 385-395
Argiolas, A., Melis, M.R., Central control of penile erection: Role of the paraventricular nucleus of the hypothalamus (2005) Prog. Neurobiol, 76, pp. 1-21
Mancuso, C., Heme oxygenase and its products in the nervous system (2004) Antioxid. Redox Signal, 6, pp. 878-887
Mancuso, C., Inhibition of heme oxygenase in the central nervous system potentiates endotoxin-induced vasopressin release in the rat (1999) J. Neuroimmunol, 99, pp. 189-194
Mancuso, C. et al. Activation of heme oxygenase and consequent carbon monoxide formation inhibits the release of arginine vasopressin from rat hypothalamic explants. Molecular linkage between heme catabolism and neuroendocrine function. Brain Res. Mol. Brain Res. 50, 267-276 (1997). This was the first paper to provide direct evidence that carbon monoxide is involved in the regulation of vasopressin release from rat hypothalamic explantsPozzoli, G., Carbon monoxide as a novel neuroendocrine modulator: Inhibition of stimulated corticotropin-releasing hormone release from acute rat hypothalamic explants (1994) Endocrinology, 135, pp. 2314-2317
Jaffrey, S.R., Erdjument-Bromage, H., Ferris, C.D., Tempst, P., Snyder, S.H., Protein S-nitrosylation: A physiological signal for neuronal nitric oxide (2001) Nature Cell Biol, 3, pp. 193-197
Choi, Y.B., Molecular basis of NMDA receptor-coupled ion channel modulation by S-nitrosylation (2000) Nature Neurosci, 3, pp. 15-21
Lipton, S.A., Singel, D.J., Stamler, J.S., Nitric oxide in the central nervous system (1994) Prog. Brain Res, 103, pp. 359-364
Mungrue, I.N., Bredt, D.S., nNOS at a glance: Implications for brain and brawn (2004) Cell Sci, 117, pp. 2627-2629
Melino, G., S-nitrosylation regulates apoptosis (1997) Nature, 388, pp. 432-433
Liu, L. & Stamler, J. S. NO: an inhibitor of cell death. Cell Death Differ. 6, 937-942 (1999)Mannick, J.B., S-Nitrosylation of mitochondrial caspases (2001) J. Cell Biol, 154, pp. 1111-1116
Tenneti, L., D'Emilia, D.M., Lipton, S.A., Suppression of neuronal apoptosis by S-nitrosylation of caspases (1997) Neurosci. Lett, 236, pp. 139-142
Zhou, P., Qian, L., Iadecola, C., Nitric oxide inhibits caspase activation and apoptotic morphology but does not rescue neuronal death (2005) J. Cereb. Blood Flow Metab, 25, pp. 348-357
Kitamura, Y., In vitro and in vivo induction of heme oxygenase-1 in rat glial cells: Possible involvement of nitric oxide production from inducible nitric oxide synthase (1998) Glia, 22, pp. 138-148
Mancuso, C., Bonsignore, A., Di Stasio, E., Mordente, A. & Motterlini, R. Bilirubin and S-nitrosothiols interaction: evidence for a possible role of bilirubin as a scavenger of nitric oxide. Biochem. Pharmacol. 66, 2355-2363 (2003). In this paper, the authors describe the ability of bilirubin to interact with S-nitrosothiolsGood, P.F., Hsu, A., Werner, P., Perl, D.P., Olanow, C.W., Protein nitration in Parkinson's disease (1998) J. Neuropathol. Exp. Neurol, 57, pp. 338-342
Mancuso, C., Mitochondrial dysfunction, free radical generation and cellular stress response in neurodegenerative disorders (2007) Front. Biosci, 12, pp. 1107-1123
Dalle-Donne, I., Scaloni, A. & Butterfield, D. A. (Eds) Redox Proteomics: From Protein Modifications to Cellular Dysfunctions and Diseases (John Wiley & Sons, New Jersey, 2006). A comprehensive treatise on the identification of oxidatively modified proteins in health and diseaseCastegna, A., Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part II: Dihydropyrimidinase- related protein 2, α-enolase and heat shock cognate 71 (2002) J. Neurochem, 82, pp. 1524-1532
Messier, C., Gagnon, M., Glucose regulation and brain aging (2000) J. Nutr. Health Aging, 4, pp. 208-213
Vanhanen, M., Soininen, H., Glucose intolerance, cognitive impairment and Alzheimer's disease (1998) Curr. Opin. Neurol, 11, pp. 673-677
Ojika, K., Tsugu, Y., Mitake, S., Otsuka, Y., Katada, E., NMDA receptor activation enhances the release of a cholinergic differentiation peptide (HCNP) from hippocampal neurons in vitro (1998) Brain Res. Dev. Brain Res, 106, pp. 173-180
Rossor, M.N., The substantia innominata in Alzheimer's disease: An histochemical and biochemical study of cholinergic marker enzymes (1982) Neurosci. Lett, 28, pp. 217-222
Giacobini, E., Cholinergic function and Alzheimer's disease (2003) Int. J. Geriatr. Psychiatry, 18, pp. S1-S5
Sun, M.K., Alkon, D.L., Carbonic anhydrase gating of attention: Memory therapy and enhancement (2002) Trends Pharmacol. Sci, 23, pp. 83-89
Browne, S.E., Beal, M.F., Oxidative damage in Huntington's disease pathogenesis (2006) Antioxid. Redox Signal, 8, pp. 2061-2073
Gu, Z., S-nitrosylation of matrix metalloproteinases: Signaling pathway to neuronal cell death (2002) Science, 297, pp. 1186-1190
Yong, V.W., Power, C., Forsyth, P., Edwards, D.R., Metalloproteinases in biology and pathology of the nervous system (2001) Nature Rev. Neurosci, 2, pp. 502-511
Yao, D., Nitrosative stress linked to sporadic Parkinson's disease: S-nitrosylation of parkin regulates its E3 ubiquitin ligase activity (2004) Proc. Natl Acad. Sci. USA, 101, pp. 10810-10814
Chung, K.K., S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function (2004) Science, 304, pp. 1328-1331
Hara, M. R. et al. Neuroprotection by pharmacologic blockade of the GAPDH death cascade. Proc. Natl Acad. Sci. USA 103, 3887-3889 (2006). This paper describes a GAPDH-SIAH1-mediated pathway for cell death and unravels a new mechanism of action for selegiline, a drug used in the treatment of Parkinson's diseaseUehara, T., S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration (2006) Nature, 441, pp. 513-517
Burnett, A.L., The role of nitric oxide in erectile dysfunction: Implications for medical therapy (2006) J. Clin. Hypertens. (Greenwich), 8 (SUPPL. 4), pp. 53-62
Redington, A.E., Modulation of nitric oxide pathways: Therapeutic potential in asthma and chronic obstructive pulmonary disease (2006) Eur. J. Pharmacol, 533, pp. 263-276
Griffiths, M.J., Evans, T.W., Inhaled nitric oxide therapy in adults (2005) N. Engl. J. Med, 353, pp. 2683-2695
Hemnes, A.R., Champion, H.C., Sildenafil, a PDE5 inhibitor, in the treatment of pulmonary hypertension (2006) Expert Rev. Cardiovasc. Ther, 4, pp. 293-300
Butterfield, D., Nutritional approaches to combat oxidative stress in Alzheimer's disease (2002) J. Nutr. Biochem, 13, p. 444
Scapagnini, G., Curcumin activates defensive genes and protects neurons against oxidative stress (2006) Antioxid. Redox Signal, 8, pp. 395-403
Kanski, J., Aksenova, M., Stoyanova, A., Butterfield, D.A., Ferulic acid antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro: Structure-activity studies (2002) J. Nutr. Biochem, 13, pp. 273-281
Kim, H.S., Inhibitory effects of long-term administration of ferulic acid on microglial activation induced by intracerebroventricular injection of β-amyloid peptide (1-42) in mice (2004) Biol. Pharm. Bull, 27, pp. 120-121
Sultana, R., Ravagna, A., Mohmmad-Abdul, H., Calabrese, V., Butterfield, D.A., Ferulic acid ethyl ester protects neurons against amyloid β-peptide (1-42)-induced oxidative stress and neurotoxicity: Relationship to antioxidant activity (2005) J. Neurochem, 92, pp. 749-758
Calabrese, V., Giuffrida Stella, A.M., Calvani, M., Butterfield, D.A., Acetylcarnitine and cellular stress response: Roles in nutritional redox homeostasis and regulation of longevity genes (2006) J. Nutr. Biochem, 17, pp. 73-88
Calabrese, V., Disruption of thiol homeostasis and nitrosative stress in the cerebrospinal fluid of patients with active multiple sclerosis: Evidence for a protective role of acetylcarnitine (2003) Neurochem. Res, 28, pp. 1321-1328
Abdul, H.M., Calabrese, V., Calvani, M., Butterfield, D.A., Acetyl-L-carnitine-induced up-regulation of heat shock proteins protects cortical neurons against amyloid-β peptide 1-42-mediated oxidative stress and neurotoxicity: Implications for Alzheimer's disease (2006) J. Neurosci. Res, 84, pp. 398-408
De Marchis, S., Modena, C., Peretto, P., Giffard, C., Fasolo, A., Carnosine-like immunoreactivity in the central nervous system of rats during postnatal development (2000) J. Comp. Neurol, 426, pp. 378-390
Calabrese, V., Protective effect of carnosine during nitrosative stress in astroglial cell cultures (2005) Neurochem. Res, 30, pp. 797-807
Preston, J.E., Hipkiss, A.R., Himsworth, D.T., Romero, I.A., Abbott, J.N., Toxic effects of β-amyloid (25-35) on immortalised rat brain endothelial cell: Protection by carnosine, homocarnosine and β-alanine (1998) Neurosci. Lett, 242, pp. 105-108
Hipkiss, A.R., Pluripotent protective effects of carnosine, a naturally occurring dipeptide (1998) Ann. NY Acad. Sci, 854, pp. 37-53
Fontana, M., Pinnen, F., Lucente, G., Pecci, L., Prevention of peroxynitrite-dependent damage by carnosine and related sulphonamido pseudodipeptides (2002) Cell. Mol. Life Sci, 59, pp. 546-551
Joshi, G., Glutathione elevation by ?-glutamylcysteine ethyl ester as a potential therapeutic strategy towards preventing oxidative stress in brain mediated by in vivo administration of adriamycin: Implications for chemobrain (2007) J. Neurosci. Res, 85, pp. 497-503
Tangpong, J., Adriamycin-induced, TNF-?-mediated central nervous system toxicity (2006) Neurobiol. Dis, 23, pp. 127-139
Silverman, D.H., Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy (2007) Breast Cancer Res. Treat, 103, pp. 303-311
Rahman, I., Biswas, S.K., Kirkham, P.A., Regulation of inflammation and redox signalling by dietary polyphenols (2006) Biochem. Pharmacol, 72, pp. 1439-1452
Sultana, R., Proteomic identification of nitrated brain proteins in amnestic mild cognitive impairment: A regional study (2007) J. Cell. Mol. Med, 11, pp. 839-851
Butterfield, D. A. et al. Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimer's disease. Neurobiol. Dis. 22, 223-232 (2006). This was the first paper to describe proteomicsidentified oxidatively modified brain proteins in mild cognitive impairment, a precursor to Alzheimer's diseaseSalerno, L., Sorrenti, V., Di Giacomo, C., Romeo, G. & Siracusa, M. A. Progress in the development of selective nitric oxide synthase (NOS) inhibitors. Curr. Pharm. Des. 8, 177-200 (2002). This paper provides useful information about the selectivity of several NOS inhibitorsMejia-Garcia, T.A., Paes-de-Carvalho, R., Nitric oxide regulates cell survival in purified cultures of avian retinal neurons: Involvement of multiple transduction pathways (2007) J. Neurochem, 100, pp. 382-394
Privalle, C., Talarico, T., Keng, T., DeAngelo, J., Pyridoxalated hemoglobin polyoxyethylene: A nitric oxide scavenger with antioxidant activity for the treatment of nitric oxide-induced shock (2000) Free Radic. Biol. Med, 28, pp. 1507-1517
Kaur, H., Interaction of bilirubin and biliverdin with reactive nitrogen species (2003) FEBS Lett, 543, pp. 113-119
Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity
At the end of the 1980s, it was clearly demonstrated that cells produce nitric oxide and that this gaseous molecule is involved in the regulation of the cardiovascular, immune and nervous systems, rather than simply being a toxic pollutant. In the CNS, nitric oxide has an array of functions, such as the regulation of synaptic plasticity, the sleep-wake cycle and hormone secretion. Particularly interesting is the role of nitric oxide as a Janus molecule in the cell death or survival mechanisms in brain cells. In fact, physiological amounts of this gas are neuroprotective, whereas higher concentrations are clearly neurotoxic.
Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity
No results.
Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity