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… 
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Early decrease of mitochondrial DNA repair enzymes in spinal motor neurons of presymptomatic transgenic mice carrying a mutant SOD1 gene

Mitochondrial targeting of human 8-oxoguanine DNA glycosylase hOGG1 is impaired by a somatic mutation found in kidney cancer.

MTH1, an Oxidized Purine Nucleoside Triphosphatase, Suppresses the Accumulation of Oxidative Damage of Nucleic Acids in the Hippocampal Microglia during Kainate-Induced Excitotoxicity

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It is shown that MTH1 efficiently suppresses the accumulation of 8-oxoG in both cellular DNA and RNA in the hippocampus, especially in microglia, caused by excitotoxicity.

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The findings implicate oxidized nucleic acid precursors in the neuropathological features of Huntington's disease and identify the utilization of oxidizeducleoside triphosphates by striatal cells as a significant contributor to the pathogenesis of this disorder.

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It is demonstrated that MTH1 protects the dopamine neurons from oxidative damage in the nucleic acids, especially in the mitochondrial DNA of striatal nerve terminals of dopamine neurons.

Pathological Interaction between DNA Repair and Mitochondrial Dysfunction in ALS

TLDR
Evidence supports either downregulation or impaired recruitment of DNA repair enzymes in both nuclear and mitochondrial genomes and suggests a complex metabolic dysregulation as a critical component in the promo-tion of the disease.

Increased oxidative damage to DNA in an animal model of amyotrophic lateral sclerosis

TLDR
Evidence is provided that in this model of ALS oixidative DNA-damage is increased and base excision-repair may be deficient and free levels of 8OHG were found to be significantly higher at 120 days of age in control mice than in G93A mice.

Accumulation of 8-oxoguanine in the cellular DNA and the alteration of the OGG1 expression during ischemia-reperfusion injury in the rat kidney.

Defense mechanism to oxidative DNA damage in glial cells

TLDR
Results indicate that the two repair enzymes to oxidative DNA damage are differentially regulated in glial cells, and that there is a difference in the expression of the repair enzymes between reactive astrocytes and oligodendrocyte.

Variants and Polymorphisms of DNA Repair

TLDR
The current knowledge on DNA repair gene variants and polymorphisms and major neurodegenerative disorders is discussed.
...

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