Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Norway; Clinic of Laboratory Medicine, St. Olavs Hospital, N-7491 Trondheim, Norway.
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Norway.
DNA Repair (Amst). 2019 Sep;81:102665. doi: 10.1016/j.dnarep.2019.102665. Epub 2019 Jul 8.
Endogenous and exogenous oxidative agents continuously damage genomic DNA, with the brain being particularly vulnerable. Thus, preserving genomic integrity is key for brain health and neuronal function. Accumulation of DNA damage is one of the causative factors of ageing and increases the risk of a wide range of neurological disorders. Base excision repair is the major pathway for removal of oxidized bases in the genome and initiated by DNA glycosylases. Emerging evidence suggest that DNA glycosylases have non-canonical functions important for genome regulation. Understanding canonical and non-canonical functions of DNA glycosylases processing oxidative base lesions modulating brain function will be crucial for the development of novel therapeutic strategies.
内源性和外源性的氧化剂会持续破坏基因组 DNA，大脑尤其容易受到损伤。因此，保持基因组的完整性是大脑健康和神经元功能的关键。DNA 损伤的积累是衰老的一个原因，并增加了多种神经疾病的风险。碱基切除修复是基因组中氧化碱基去除的主要途径，由 DNA 糖苷酶启动。新出现的证据表明，DNA 糖苷酶具有对基因组调控很重要的非经典功能。了解 DNA 糖苷酶处理氧化碱基损伤以调节大脑功能的经典和非经典功能，对于开发新的治疗策略至关重要。
