DNA repair in aging rat neurons

Rao, K. S.

doi:10.1016/j.neuroscience.2006.09.032

Cited by 60 publications

(31 citation statements)

References 57 publications

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“…Furthermore, it has been proposed that accumulation of nDNA damage (or, in a broader sense, the inability of neurons to appropriately handle nDNA damage) serves as molecular trigger in the etiology of age-related neurodegenerative disorders [92][93][94][95]). This aspect will be discussed in Section 6.…”

Section: Age-related Accumulation Of Ndna Damage and Decline In Ndna mentioning

confidence: 99%

“…In this regard it is important to note that several studies have provided evidence that nDNA damage plays an important role in AD as well as in other neurodegenerative diseases [93,[148][149][150]. For instance, many TUNEL-positive neurons are detected in postmortem brains from patients with AD [37,151] and a subset of these cells is known to accumulate truncated tau [152].…”

Section: Accumulation Of Ndna Damage or Neuron Loss: Implications Formentioning

confidence: 99%

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Accumulation of nuclear DNA damage or neuron loss: Molecular basis for a new approach to understanding selective neuronal vulnerability in neurodegenerative diseases

et al. 2008

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According to a long-standing hypothesis, aging is mainly caused by accumulation of nuclear (n) DNA damage in differentiated cells such as neurons due to insufficient nDNA repair during lifetime. In line with this hypothesis it was until recently widely accepted that neuron loss is a general consequence of normal aging, explaining some degree of decline in brain function during aging. However, with the advent of more accurate procedures for counting neurons, it is currently widely accepted that there is widespread preservation of neuron numbers in the aging brain, and the changes that do occur are relatively specific to certain brain regions and types of neurons. Whether accumulation of nDNA damage and decline in nDNA repair is a general phenomenon in the aging brain or also shows cell-type specificity is, however, not known. It has not been possible to address this issue with the biochemical and molecular-biological methods available to study nDNA damage and nDNA repair. Rather, it was the introduction of autoradiographic methods to study quantitatively the relative amounts of nDNA damage (measured as nDNA single-strand breaks) and nDNA repair (measured as unscheduled DNA synthesis) on tissue sections that made it possible to address this question in a cell-type-specific manner under physiological conditions. The results of these studies revealed a formerly unknown inverse relationship between age-related accumulation of nDNA damage and age-related impairment in nDNA repair on the one hand, and the age-related, selective, loss of neurons on the other hand. This inverse relation may not only reflect a fundamental process of aging in the central nervous system but also provide the molecular basis for a new approach to understand the selective neuronal vulnerability in neurodegenerative diseases, particularly Alzheimer's disease.

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Section: Age-related Accumulation Of Ndna Damage and Decline In Ndna mentioning

confidence: 99%

Section: Accumulation Of Ndna Damage or Neuron Loss: Implications Formentioning

confidence: 99%

Accumulation of nuclear DNA damage or neuron loss: Molecular basis for a new approach to understanding selective neuronal vulnerability in neurodegenerative diseases

et al. 2008

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“…Accumulation of oxidative genome damage is a unifying feature of most pathologies associated with metal toxicity (13)(14)(15). Redox-cycling iron and copper could generate O 2 free radicals (ROS) via a Fenton reaction, which oxidizes cellular components, including DNA.…”

mentioning

confidence: 99%

Specific Inhibition of NEIL-initiated Repair of Oxidized Base Damage in Human Genome by Copper and Iron

Hegde

Holthauzen

et al. 2010

Journal of Biological Chemistry

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“…A general reduction in DNA repair activity has been associated with brain aging in humans and rodents raising the possibility that this is a normal aspect of aging (Intano et al 2003;Lu et al 2004;Imam et al 2006;Gorbunova et al 2007;Rao 2007;Rutten et al 2007). However, a correlative relationship between repair activity and aging doesn't necessarily imply that an assayable decrease in enzyme activity would be associated with increased DNA lesions or accumulation of mutations.…”

Section: Perspective and Conclusionmentioning

confidence: 99%

DNA strand breaks, neurodegeneration and aging in the brain

Katyal

McKinnon

2008

Mechanisms of Ageing and Development

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Defective responses to DNA single-or double-strand breaks can result in neurological disease, underscoring the critical importance of DNA repair for neural homeostasis. Human DNA repairdeficient syndromes are generally congenital, in which brain pathology reflects the consequences of developmentally incurred DNA damage. Although, it is unclear to what degree DNA strandbreak repair defects in mature neural cells contributes to disease pathology. However, DNA single-strand breaks are a relatively common lesion which if not repaired can impact cells via interference with transcription. Thus, this lesion, and probably to a lesser extent DNA double strand breaks, may be particularly relevant to aging in the neural cell population. In this review we will examine the consequences of defective DNA strand break repair towards homeostasis in the brain. Further, we also consider the utility of mouse models as reagents to understand the connection between DNA strand breaks and aging in the brain.

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DNA repair in aging rat neurons

Cited by 60 publications

References 57 publications

Accumulation of nuclear DNA damage or neuron loss: Molecular basis for a new approach to understanding selective neuronal vulnerability in neurodegenerative diseases

Accumulation of nuclear DNA damage or neuron loss: Molecular basis for a new approach to understanding selective neuronal vulnerability in neurodegenerative diseases

Specific Inhibition of NEIL-initiated Repair of Oxidized Base Damage in Human Genome by Copper and Iron

DNA strand breaks, neurodegeneration and aging in the brain

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