Department of Environment and Primary Prevention, Istituto Superiore di Sanita', Viale Regina Elena 299, 00161 Rome, Italy.
Mutat Res. 2010 Nov 28;703(1):59-65. doi: 10.1016/j.mrgentox.2010.06.008. Epub 2010 Jun 19.
Oxidative DNA damage can be the consequence of endogenous metabolic processes and exogenous insults and several DNA repair enzymes provide protection against the toxic effects of oxidized DNA bases. Here we review the increasing knowledge on the relationship between an oxidized dNTPs pool and genome instability. The review also describes some important progress toward understanding the role of oxidative DNA damage and its repair in neurodegenerative diseases. In particular the hMTH1 hydrolase destroys oxidized nucleic acid precursors to prevent their harmful incorporation into DNA and RNA. Based on results obtained in our transgenic mouse overexpressing hMTH1 in the brain we discussed the mechanisms by which this hydrolase protects against neurodegeneration in Huntington disease models.
氧化 DNA 损伤可能是内源性代谢过程和外源性损伤的结果，几种 DNA 修复酶为氧化 DNA 碱基的毒性作用提供了保护。在这里，我们回顾了关于氧化 dNTP 池与基因组不稳定性之间关系的日益增长的知识。该综述还描述了一些理解氧化 DNA 损伤及其修复在神经退行性疾病中的作用的重要进展。特别是 hMTH1 水解酶破坏氧化的核酸前体，以防止它们有害地掺入 DNA 和 RNA 中。基于我们在大脑中过表达 hMTH1 的转基因小鼠中获得的结果，我们讨论了这种水解酶如何防止亨廷顿病模型中的神经退行性变。
