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Editorial [Hot Topic: Nitric Oxide: Implications for the Etiology & Treatment of Central Nervous System Disorders (Guest Editor: Giuseppe Di Giovanni)]

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More the 100,000 papers have been published about nitric oxide (NO) since its discovery 24 years ago. NO is a distinct cell-to-cell signalling molecule which is found in nearly all the tissues of the body and central nervous system (CNS).

Interest in NO grew when its release from endothelial cells lining blood vessels was shown to cause relaxation of the underlying smooth muscle, thereby affecting blood flow and pressure. When, in 1998, Furchgott, Ignarro and Murad won the Nobel Prize for Physiology or Medicine for their contribution to the study of NO its fame peaked. Also in 1998, NO was identified as the mysterious substance produced following activation of N-methyl-D-aspartic acid (NMDA) glutamatergic receptors. An enormous amount of data on the role of NO has been collected since then. Indeed, it is hard to find a disease which is not associated with altered NO homeostasis.

NO is a gas produced from the amino acid L-arginine by members of the NO synthase (NOS) family of proteins, respectively, as endothelial, neuronal, and inducible NO synthases. NO is involved in smooth muscle relaxation, neural communication, and immune defence.

In the CNS, NO is a key physiological signalling molecule. A number of studies have identified high levels of nNOS in many areas of the brain. It occurs also in astrocytes and cerebral blood vessels. Some of the NO effects are mediated by stimulation of soluble guanylyl cyclase and it product cyclic guanosine monophosphate (cGMP).

However, it has also been clearly shown that NO becomes noxious if produced in excess. Toxic compounds can be formed as a result of NO undergoing oxidative-reductive reactions when a cell is in a pro-oxidant state. Both NO and these toxic compounds have been implicated in the pathogenesis of neurodegenerative disorders. Indeed, the cellular damage in neurodegenerative disorders could be caused by NO and peroxynitrites, the latter formed by the reaction between NO and a superoxide anion. This scenario is common to Alzheimer's disease (AD) and Parkinson's disease (PD), pain, atherosclerosis, epilepsy and septic shock. NO has also been suggested to have a significant role in many different psychiatric disorders such as depression, anxiety, schizophrenia. Despite the enormous amount of progress we have made in terms of understanding the aetiology of NO-related diseases in the last twenty years, important questions about the role of NO in the CNS remain unanswered.

Given the broad range of functions of NO, this Special Issue will concentrate on some of the physiological and pathological implications of NO activity in the regulation of the CNS. In particular, it focuses on the multifaceted functions of NO in various neuropsychiatric disorders. This Special Issue deals with this hot topic and it is produced by leading groups in the neuroscience field with the aim of summarizing recent advances in genetic, epidemiological, molecular and cellular biology research that have increased our knowledge of the mechanisms by which NO gives rise to degenerative processes and, in general, to alterations of nervous system structure and function. While covering the latest research in schizophrenia, AD, PD, epilepsy and brain tumours, for obvious reasons, this special issue cannot be exhaustive. Indeed, it is impossible to include reviews highlighting all the vast number of different CNS diseases in which NO seems to play a role. I hope that more volumes on the subject will be possible in the future.....
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Document Type: Research Article

Publication date: 2011-11-01

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  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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