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e-Article

Impact of Oxidative DNA Damage and the Role of DNA Glycosylases in Neurological Dysfunction.
Document Type
Article
Source
International Journal of Molecular Sciences. Dec2021, Vol. 22 Issue 23, p12924. 1p.
Subject
*DNA glycosylases
*DNA damage
*DNA ligases
*REACTIVE oxygen species
*OXYGEN consumption
Language
ISSN
1661-6596
Abstract
The human brain requires a high rate of oxygen consumption to perform intense metabolic activities, accounting for 20% of total body oxygen consumption. This high oxygen uptake results in the generation of free radicals, including reactive oxygen species (ROS), which, at physiological levels, are beneficial to the proper functioning of fundamental cellular processes. At supraphysiological levels, however, ROS and associated lesions cause detrimental effects in brain cells, commonly observed in several neurodegenerative disorders. In this review, we focus on the impact of oxidative DNA base lesions and the role of DNA glycosylase enzymes repairing these lesions on brain function and disease. Furthermore, we discuss the role of DNA base oxidation as an epigenetic mechanism involved in brain diseases, as well as potential roles of DNA glycosylases in different epigenetic contexts. We provide a detailed overview of the impact of DNA glycosylases on brain metabolism, cognition, inflammation, tissue loss and regeneration, and age-related neurodegenerative diseases based on evidence collected from animal and human models lacking these enzymes, as well as post-mortem studies on patients with neurological disorders. [ABSTRACT FROM AUTHOR]