Book contents
- Frontmatter
- Contents
- List of contributors
- Preface
- Part I Basic aspects of neurodegeneration
- 1 Endogenous free radicals and antioxidants in the brain
- 2 Biological oxidants and therapeutic antioxidants
- 3 Mitochondria, metabolic inhibitors and neurodegeneration
- 4 Excitoxicity and excitatory amino acid antagonists in chronic neurodegenerative diseases
- 5 Glutamate transporters
- 6 Calcium binding proteins in selective vulnerability of motor neurons
- 7 Apoptosis in neurodegenerative diseases
- 8 Neurotrophic factors
- 9 Protein misfolding and cellular defense mechanisms in neurodegenerative diseases
- 10 Neurodegenerative disease and the repair of oxidatively damaged DNA
- 11 Compounds acting on ion channels
- 12 The role of nitric oxide and PARP in neuronal cell death
- 13 Copper and zinc in Alzheimer's disease and amyotrophic lateral sclerosis
- 14 The role of inflammation in Alzheimer's disease neuropathology and clinical dementia. From epidemiology to treatment
- 15 Selected genetically engineered models relevant to human neurodegenerative disease
- 16 Toxic animal models
- 17 A genetic outline of the pathways to cell death in Alzheimer's disease, Parkinson's disease, frontal dementias and related disorders
- 18 Neurophysiology of Parkinson's disease, levodopa-induced dyskinesias, dystonia, Huntington's disease and myoclonus
- Part II Neuroimaging in neurodegeneration
- Part III Therapeutic approaches in neurodegeneration
- Normal aging
- Part IV Alzheimer's disease
- Part VI Other Dementias
- Part VII Parkinson's and related movement disorders
- Part VIII Cerebellar degenerations
- Part IX Motor neuron diseases
- Part X Other neurodegenerative diseases
- Index
- References
12 - The role of nitric oxide and PARP in neuronal cell death
from Part I - Basic aspects of neurodegeneration
Published online by Cambridge University Press: 04 August 2010
- Frontmatter
- Contents
- List of contributors
- Preface
- Part I Basic aspects of neurodegeneration
- 1 Endogenous free radicals and antioxidants in the brain
- 2 Biological oxidants and therapeutic antioxidants
- 3 Mitochondria, metabolic inhibitors and neurodegeneration
- 4 Excitoxicity and excitatory amino acid antagonists in chronic neurodegenerative diseases
- 5 Glutamate transporters
- 6 Calcium binding proteins in selective vulnerability of motor neurons
- 7 Apoptosis in neurodegenerative diseases
- 8 Neurotrophic factors
- 9 Protein misfolding and cellular defense mechanisms in neurodegenerative diseases
- 10 Neurodegenerative disease and the repair of oxidatively damaged DNA
- 11 Compounds acting on ion channels
- 12 The role of nitric oxide and PARP in neuronal cell death
- 13 Copper and zinc in Alzheimer's disease and amyotrophic lateral sclerosis
- 14 The role of inflammation in Alzheimer's disease neuropathology and clinical dementia. From epidemiology to treatment
- 15 Selected genetically engineered models relevant to human neurodegenerative disease
- 16 Toxic animal models
- 17 A genetic outline of the pathways to cell death in Alzheimer's disease, Parkinson's disease, frontal dementias and related disorders
- 18 Neurophysiology of Parkinson's disease, levodopa-induced dyskinesias, dystonia, Huntington's disease and myoclonus
- Part II Neuroimaging in neurodegeneration
- Part III Therapeutic approaches in neurodegeneration
- Normal aging
- Part IV Alzheimer's disease
- Part VI Other Dementias
- Part VII Parkinson's and related movement disorders
- Part VIII Cerebellar degenerations
- Part IX Motor neuron diseases
- Part X Other neurodegenerative diseases
- Index
- References
Summary
Nitric oxide
Nitric oxide (NO) is a novel neuronal messenger molecule that is not confined to the synaptic cleft and can mediate rapid signaling by diffusing freely in three dimensions to act throughout local regions of neural tissue (Dawson & Dawson, 1998). NO can be generated in most tissues in the body and was first identified as endothelium-derived relaxing factor (EDRF) in blood vessels where it is the major regulator of vascular tone (Furchgott & Zawadzki, 1980; Palmer et al., 1987; Kilbourn & Belloni, 1990; Ignarro, 1991). NO is produced by the enzymatic conversion of L-arginine to L-citrulline by nitric oxide synthase (NOS). In the NO biosynthetic scheme, L-arginine is first oxygenated to the intermediate NG-hydroxy-L-arginine, which is then oxygenated to produce NO and L-citrulline. NO has a short half-life due to the pervasive action of superoxide (Palmer et al., 1987). There are three isoforms of NOS. Two isoforms are expressed constitutively (neuronal; nNOS, endothelial; eNOS) and one that expressed only after induction (inducible; iNOS) (Fujisawa et al., 1994; Chartrain et al., 1994; Marsden et al., 1993). Both the constitutive and inducible forms are tetrahydrobiopterin (BH4) dependent (Tayeh & Marletta, 1989; Kwon et al., 1989). The constitutive isoforms, nNOS and eNOS are Ca2+/calmodulin regulated and thus NO generation is dependent on calcium signaling events. However, iNOS is Ca2+/calmodulin independent and therefore NO is generated from iNOS upon protein expression. NO generation from iNOS is regulated by the duration of mRNA expression for iNOS (Dawson & Dawson, 1998).
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- Neurodegenerative DiseasesNeurobiology, Pathogenesis and Therapeutics, pp. 146 - 156Publisher: Cambridge University PressPrint publication year: 2005