• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



Parkinson's Disease and Related Disorders

開催日 2014/9/11
時間 16:00 - 17:00
会場 Poster / Exhibition(Event Hall B)

8- オキソグアニンが老化マウスにおけるドーパミン神経変性を引き起こすメカニズム
Mechanism by which 8-oxoguanine causes dopaminergic neurodegeneration in aged mice

  • P1-306
  • 盛 子敬 / Zijing Sheng:1,2 中別府 雄作 / Yusaku Nakabeppu:1,2 
  • 1:九州大学・生体防御医学研究所・個体機能制御学部門・脳機能制御学分野 / Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University 2:九州大学・ヌクレオチドプール研究センター / Nucleotide pool research center, Kyushu University 

8-Oxoguanine, a major oxidized base lesion, has been inferred to be involved in the neurodegenerative diseases. To counteract oxidative damage to nucleic acids, MTH1 hydrolyzes oxidized purine nucleoside triphosphates, thus sanitizing nucleotide pools. OGG1, an 8-oxoguanine DNA glycosylase, prevents buildup of 8-oxoguanine in both nuclear and mitochondrial genomes. Our previous studies showed that MTH1-deficient young mice exhibited a greater accumulation of 8-oxoguanine after MPTP administration (Yamaguchi et al., Cell Death Differ, 2006). Aging is a risk factor for the development and progression of Parkinson's disease (PD), however, the mechanism by which 8-oxoguanine causes dopamine neurodegeneration in aged mice, has yet to be clarified.
In the present study, first, we observed that expression of MTH1 and OGG1 is abundantly detected in substantia nigra. Then, double-immunodetection with neuronal markers revealed that dopaminergic neurons co-express both MTH1 and OGG1. Furthermore, we show that the MPTP-treated mutant mice lacking MTH1 and OGG1 exhibit abnormal behavior compared to wild-type mice. These results strongly suggest that MTH1 and OGG1 contribute to the maintenance of genomic integrity in dopaminergic neurons, and play an important role in PD pathogenesis.

Copyright © Neuroscience2014. All Right Reserved.