Impairment of mitochondrial DNA repair enzymes against accumulation of 8-oxo-guanine in the spinal motor neurons of amyotrophic lateral sclerosis

@article{Kikuchi2002ImpairmentOM,
  title={Impairment of mitochondrial DNA repair enzymes against accumulation of 8-oxo-guanine in the spinal motor neurons of amyotrophic lateral sclerosis},
  author={Hitoshi Kikuchi and Akiko Furuta and Kenichi Nishioka and Satoshi O. Suzuki and Yusaku Nakabeppu and Toru Iwaki},
  journal={Acta Neuropathologica},
  year={2002},
  volume={103},
  pages={408-414}
}
Abstract. Oxidative stress plays an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). In the present study, we investigated the expression of two major human enzymes that prevent errors caused by 8-oxoguanine (8-oxoG), a mitochondrial form of 8-oxoG DNA glycosylase (hOGG1) and oxidized purine nucleoside triphosphatase (hMTH1). We also investigated the relationship between their expression and the 8-oxoG accumulation observed in the large motor neurons of the lumbar… Expand
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References

SHOWING 1-10 OF 41 REFERENCES
Oxidative damage to mitochondrial DNA in spinal motoneurons of transgenic ALS mice.
TLDR
Data suggest that an oxidative damage to mitochondrial DNA is happening in spinal motoneurons of the Tg mice from very early stage of the disease, and may be involved in the mechanism of the subsequent motoneuron death in this model. Expand
Oxidative Stress and Motor Neurone Disease
TLDR
Future research will need to identify the aspects of the molecular and physiological phenotype of human motor neurones that makes them susceptible to degeneration in MND, and to identify those genetic and environmental factors which combine to cause this disease in individuals and in familial pedigrees. Expand
Nonoxidative protein glycation is implicated in familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation
TLDR
The present results indicate that oxidative reactions are involved in the disease processes of sporadic ALS, while there is no evidence for increased oxidative damage except for CML deposition in the familial ALS spinal cords. Expand
Parkinson's disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons.
TLDR
Results suggest that oxidative damage to cytoplasmic nucleic acid is selectively increased in midbrain, especially the SN, of PD patients and much less so in MSA-P and DLB patients. Expand
Increased 8‐oxo‐dGTPase in the mitochondria of substantia nigral neurons in Parkinson's disease
TLDR
The results suggest that hMTH1 might be a useful marker of oxidative Stress and can be used to explore the relation between such oxidative stress and genomic instability. Expand
RNA Oxidation Is a Prominent Feature of Vulnerable Neurons in Alzheimer’s Disease
TLDR
Surprisingly, the oxidized nucleoside was associated predominantly with RNA because immunoreaction was diminished greatly by preincubation in RNase but only slightly by DNase, the first evidence of increased RNA oxidation restricted to vulnerable neurons in AD. Expand
Intracellular Localization of 8-Oxo-dGTPase in Human Cells, with Special Reference to the Role of the Enzyme in Mitochondria (*)
TLDR
The 8-oxo-dGTPase encoded by MTH1 gene is localized in mitochondria and cytosol, mainly located in cytosolic and mitochondrial soluble fractions of Jurkat cells, a human T-cell leukemia line. Expand
Evidence of Increased Oxidative Damage in Both Sporadic and Familial Amyotrophic Lateral Sclerosis
TLDR
Immunohistochemical studies showed increased neuronal staining for hemeoxygenase‐1, malondialdehyde‐modified protein, and OH8dG in both SALS and FALS spinal cord, providing further evidence that oxidative damage may play a role in the pathogenesis of neuronal degeneration in both FALS and SALS. Expand
Evidence against increased oxidative DNA-damage in Down syndrome
TLDR
It is concluded that the results provide evidence against an increased reactive oxygen species (ROS) induced damage to nDNA in DS and AD. Expand
Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis
TLDR
It was found that oral administration of creatine produced a dose-dependent improvement in motor performance and extended survival in G93A transgenic mice, and it protected mice from loss of both motor neurons and substantia nigra neurons at 120 days of age. Expand
...
1
2
3
4
5
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