Bosshard Matthias, Markkanen Enni, van Loon Barbara
Institute for Veterinary Biochemistry and Molecular Biology, University of Zürich-Irchel, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Int J Mol Sci. 2012 Nov 30;13(12):16172-222. doi: 10.3390/ijms131216172.
Relatively low levels of antioxidant enzymes and high oxygen metabolism result in formation of numerous oxidized DNA lesions in the tissues of the central nervous system. Accumulation of damage in the DNA, due to continuous genotoxic stress, has been linked to both aging and the development of various neurodegenerative disorders. Different DNA repair pathways have evolved to successfully act on damaged DNA and prevent genomic instability. The predominant and essential DNA repair pathway for the removal of small DNA base lesions is base excision repair (BER). In this review we will discuss the current knowledge on the involvement of BER proteins in the maintenance of genetic stability in different brain regions and how changes in the levels of these proteins contribute to aging and the onset of neurodegenerative disorders.
相对较低水平的抗氧化酶和较高的氧代谢会导致中枢神经系统组织中形成大量氧化的DNA损伤。由于持续的基因毒性应激，DNA损伤的积累与衰老以及各种神经退行性疾病的发展都有关联。不同的DNA修复途径已经进化出来，以成功作用于受损DNA并防止基因组不稳定。用于去除小的DNA碱基损伤的主要且关键的DNA修复途径是碱基切除修复（BER）。在本综述中，我们将讨论关于BER蛋白参与不同脑区遗传稳定性维持的当前知识，以及这些蛋白水平的变化如何导致衰老和神经退行性疾病的发生。
