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Handbook of Neurochemistry and Molecular Neurobiology pp 223–247Cite as

Nitric Oxide Synthases in Brain Function

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Abstract:

The nitric oxide synthase (NOS) enzymes, three gene products that are highly homologous, are variously expressed in the nervous system. Gene regulation is complex, and they are the only flavoheme enzymes that require tetrahydrobiopterin (BH4) as a redox cofactor. The nNOS and eNOS isoforms are constitutive enzymes found typically in some neurons and in the endothelium, respectively, while iNOS is transcriptionally activated in response to injury and infection. Distinct N‐ and C‐terminal motifs in the NOS proteins target these enzymes to discrete cellular compartments where they associate with specific scaffold and cytoskeletal proteins. Further oxidation of nitric oxide (NO) generates a wide variety of products that can react with DNA and proteins, resulting in a short‐term change and also long‐lived effects on gene expression, cell cycle, and differentiation. On the basis of the phenotype of gene‐deficient mice, and the use of enzyme inhibitors with only partial selectivity, roles for reactive nitrogen species (RNS) have been invoked in almost every aspect of nervous system function and in the pathology that accompanies acute injury and degeneration. This chapter focuses on the NOS enzymes, generation of RNS and their molecular targets, and involvement in neurodegeneration, acute injury, and the host response to infection.

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Abbreviations

AD:

Alzheimer's disease

ALS:

amyotropic lateral sclerosis

BBB:

blood–brain barrier

BH4:

tetrahydrobiopterin

CSF:

colony stimulating factor

COX:

cyclooxygenase

EAE:

experimental allergic encephalomyelitis

IFN:

interferon

IL:

interleukin

LTP:

long‐term potentiation

MS:

multiple sclerosis

NO:

nitric oxide

NOS:

nitric oxide synthase

NT:

nitrotyrosine

ONOO− :

peroxynitrite

PD:

Parkinson's disease

PDZ:

PSD‐95/discs large/zona occludens‐1

PSD:

postsynaptic density

RNS:

reactive nitrogen species

sGC:

soluble guanylyl cyclase

SNO:

S‐nitrosothiol

SOD:

superoxide dismutase

TBI:

traumatic brain injury

TNF:

tumor necrosis factor

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Acknowledgments

SM receives grant support from USPHS‐NIH, The Wellcome Trust, BBSRC, and MRC (UK). We are grateful to Drs. Keren Bielby‐Clarke, Despina Constantin, Claire Gibson, and Nigel Jones for valuable discussions.

Authors
  1. S. Murphy
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  2. T. Coughlan
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, Newyork, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurology (Division of Neurochemistry and Neurobiology), University of Iowa College of Medicine and Veterans Administration Medical Center, 52242, lowa, lowa, USA

    Ramon Lim

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Murphy, S., Coughlan, T. (2006). Nitric Oxide Synthases in Brain Function. In: Lajtha, A., Lim, R. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30381-9_11

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