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
10 - Neurodegenerative disease and the repair of oxidatively damaged DNA
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
Free radicals and oxidative damage to DNA
In addition to endogenous sources of free radicals, such as those derived from normal metabolism (see Chapter 1), pathophysiological or environmental events may also generate free radicals. Cellular biomolecules, including nucleic acids, proteins and lipids are all targets for these damaging species. Reactive oxygen species (ROS) are of particular interest. Enzymic and non-enzymic antioxidants (discussed in Chapter 2) contribute to the limit on the extent to which ROS are produced, and hence their interaction with cellular components. If the balance between the anti- and pro-oxidant factors is altered in favour of the latter, a condition of oxidative stress arises, with a concomitant increase in biomolecule modification. Given its central role in cellular events, modification of DNA, for example 8-hydroxyguanine (8-OH-Gua), and thymine glycol (Tg), has been the subject of intense study. Such lesions may have a plethora of effects, most notably mutation, but also replicative block, deletions, microsatellite instability and loss of heterozygosity, as well as various epigenetic effects (for review see Cooke et al., 2003). Furthermore, a great deal of literature exists that describes elevated levels of lesions in a variety of diseases, suggesting that the induction of damage is an important event in pathogenesis (for review, see Cooke et al., 2003). Unlike oxidatively modified lipids and proteins, which may be removed and replaced as part of normal turnover, DNA needs to be repaired, and intense study has revealed much about the processes that maintain genome integrity.
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- Neurodegenerative DiseasesNeurobiology, Pathogenesis and Therapeutics, pp. 131 - 140Publisher: Cambridge University PressPrint publication year: 2005