Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment

Wang, Jianquan; Markesbery, William R.; Lovell, Mark A.

doi:10.1111/j.1471-4159.2005.03615.x

Cited by 239 publications

(191 citation statements)

References 60 publications

(164 reference statements)

Supporting

Mentioning

175

Contrasting

Unclassified

Order By: Relevance

“…Although the use of phenol during nucleic acid isolation has been suggested to contribute to artifactual oxidation, Wang et al [26] demonstrated that detectable DNA lesions were not significantly different when extracted with a phenol:chloroform extraction compared to the popular NaI based 'salting out' method consistent with the findings of Rehamn et al [46]. Furthermore, atmospheric oxygen was excluded during nucleic acid derivatization and carried out at room temperature to minimize artifactual oxidation [46][47][48].…”

Section: Discussionsupporting

confidence: 73%

“…Derivatized samples were analyzed using an Agilent 7890A gas chromatograph on a HP-5ms capillary column (0.25 mm internal diameter, 0.25 μm film thickness, and 30 m length; Hewlett Packard, Palo Alto, CA, USA) as previously described by Wang et al [26,37]. Derivatized nitrogenous base spectra were acquired in SIM mode at the following m/z ratios: 443 (8-[8- (5OHC)).…”

Section: Gas Chromatography/mass Spectrometry (Gc/ms) With Selective mentioning

confidence: 99%

“…For analysis, RNA (100 μg) samples were prepared for GC/MS analysis as previously described by Wang et al [26,37]. …”

Section: Rna Derivatizationmentioning

confidence: 99%

“…However, modification of guanine is considered the preeminent marker of nucleic acid oxidation because of its low reduction potential. Levels of oxidized guanine have been reported to be significantly increased in both nDNA [24][25][26][27] and mtDNA [26] in the vulnerable brain regions in AD.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Increased Oxidative Damage in RNA in Alzheimer’s Disease Progression

Lovell¹

2014

J Anal Bioanal Tech

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 73%

Section: Gas Chromatography/mass Spectrometry (Gc/ms) With Selective mentioning

confidence: 99%

“…For analysis, RNA (100 μg) samples were prepared for GC/MS analysis as previously described by Wang et al [26,37]. …”

Section: Rna Derivatizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Increased Oxidative Damage in RNA in Alzheimer’s Disease Progression

Lovell¹

2014

J Anal Bioanal Tech

View full text Add to dashboard Cite

“…Accumulating evidence supports a role for oxidative stress in the pathogenesis of neuronal degeneration and death in AD (5)(6)(7)(8). The evidence supporting oxidative stress in AD comes largely from postmortem samples and includes increased lipid peroxidation, decreased polyunsaturated fatty acids (9)(10)(11)(12), increased protein oxidation (13,14), and DNA oxidation (15,16). The addition of exogenous Aβ also increases formation of free radicals and oxidative injury in in vitro studies (17,18).…”

mentioning

confidence: 99%

Rapid cell death is preceded by amyloid plaque-mediated oxidative stress

Xie

Hou

Jiang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

139

120

View full text Add to dashboard Cite

Neuronal loss is the ultimate outcome in a variety of neurodegenerative diseases and central nerve system disorders. Understanding the sequelae of events that leads to cell death would provide insight into neuroprotective approaches. We imaged neurons in the living brain of a mouse model of Alzheimer's disease that overexpresses mutant human amyloid precursor protein and presenilin 1 and followed the death of individual neurons in real time. This mouse model exhibited limited neurodegeneration and atrophy, but we were able to identify a small fraction of vulnerable cells that would not have been detectable by using standard approaches. By exploiting a genetically encoded reporter of oxidative stress, we identified susceptible neurons by their increased redox potential. The oxidative stress was most dramatic in neurites near plaques, propagated to cell bodies, and preceded activation of caspases that led to cell death within 24 h. Thus, local oxidative stress surrounding plaques contributes to longrange toxicity and selective neuronal death in Alzheimer's disease.in vivo imaging | reduction-oxidation sensitive GFP A lzheimer's disease (AD) is underscored by neurodegeneration and is the most common form of dementia. The pathological hallmarks of this disease include amyloid plaques, neurofibrillary tangles, and neuronal loss. Early-onset familial AD is caused by genetic mutations of amyloid precursor protein (APP) or presenilin 1 and 2 (PS1 and PS2). Although recent genetic studies have revealed risk factors for late onset AD, the pathogenic pathways for sporadic AD remain largely unknown. The development of mouse models of AD that develop senile plaques similar to those found in AD patients was a critical step in identifying the role of amyloid β (Aβ) on neuronal function. A major disappointment of most of the mouse models is the lack of overt neuronal loss that is a hallmark of the human disease. Many, in fact, have used this lack of neuronal death as evidence that amyloid is not relevant to dementia in AD. We and others (1-4) have identified structural and functional alterations of neurons in the brains of APP mice that implicate amyloid-mediated toxicity, but we have never detected neuronal death. The ability to monitor cell death in an experimental model provides the opportunity to intervene with neuroprotective agents that could be applied to the spectrum of neurodegenerative diseases and CNS disorders.We were able to identify vulnerable cells by quantitatively imaging the redox potential of neurons in the living brain. Our hypothesis was that amyloid-mediated increases in oxidative stress are the initiators of the toxic cascade that leads to cell loss. Accumulating evidence supports a role for oxidative stress in the pathogenesis of neuronal degeneration and death in AD (5-8). The evidence supporting oxidative stress in AD comes largely from postmortem samples and includes increased lipid peroxidation, decreased polyunsaturated fatty acids (9-12), increased protein oxidation (13,14), and DNA oxidation (15, ...

show abstract

Damage to Lipids, Proteins, DNA, and RNA in Mild Cognitive Impairment

Markesbery¹,

Lovell²

2007

Arch Neurol

Self Cite

161

131

View full text Add to dashboard Cite

ree radical-mediated oxidative damage is thought to play a role in the pathogenesis of Alzheimer disease. Previous studies have shown oxidative damage to lipids, proteins, DNA, and RNA in multiple brain regions in late-stage Alzheimer disease. Recent studies on patients with amnestic mild cognitive impairment who have undergone autopsy have shown increased lipid peroxidation as well as protein, DNA, and RNA oxidation in multiple brain regions. These studies establish oxidative damage as an early event in the pathogenesis of Alzheimer disease that can serve as a therapeutic target to slow the progression or perhaps the onset of the disease.

show abstract

Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment

Cited by 239 publications

References 60 publications

Increased Oxidative Damage in RNA in Alzheimer’s Disease Progression

Increased Oxidative Damage in RNA in Alzheimer’s Disease Progression

Rapid cell death is preceded by amyloid plaque-mediated oxidative stress

Damage to Lipids, Proteins, DNA, and RNA in Mild Cognitive Impairment

Contact Info

Product

Resources

About