Nitric oxide : implications for the etiology & treatment of central nervous system disorders

Abstract

Neurons are typically post-mitotic cells. This means that they are expected to have a life span comparable to that of their carriers. Unfortunately, sometimes, they die prematurely as a result of complex processes known as “neurodegeneration”. Neurodegenerative diseases are now generally considered a group of disorders that seriously and progressively impair the functions of the nervous system through causing the selective neuronal vulnerability of specific brain regions. Neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer Disease (AD), Multiple Sclerosis (MS), and prion disease represent several distinct categories of disease and each manifests its own unique symptoms. However, the diseases share several common features, particularly the aggregation and deposition of abnormal proteins. Neurodegenerative disorders are associated with high morbidity, and few or no effective treatments have been available until now. Neurodegenerative diseases represent a threat to mankind in a variety of guises and induce chronic suffering and debilitation in about 2% of the worldwide population. Moreover, the increase in lifespan of western populations will mean that these neurodegenerative diseases will become more common. Consequently, it is estimated that the number of PD patients will double to between 8.7 and 9.3 million by 2030. As a group, these disorders are a major burden on health care systems compared with other causes of death and the costs of treatment are expected to rise sharply. Despite the enormous amount of progress we have made in terms of understanding the aetiologies of these diseases in the last few years, important questions remain unanswered. This special number deals with this hot topic and is produced by leading groups in the neuroscience field with the aim of summarizing recent advances in genetic, epideniological, molecular and cellular biology research that have increased our knowledge of the mechanisms that give rise to degenerative processes and, in general, to alterations of the structure and function of the nervous system. These contributions give insight into new pharmacological therapies for their treatment and review new and old drugs aimed at interrupting or at attenuating different pathogenic pathways of neurodegeneration and/or at ameliorating symptoms. The pharmaceutical industry faces arguably its most difficult challenge in attempting to develop therapeutics for neurodegenerative disease. The development of disease-modifying therapeutics that addresses the principal causes of neurodegenerative disease is still in its infancy.