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Impact of Oxidative DNA Damage and the Role of DNA Glycosylases in Neurological Dysfunction

Authors :
Jing Ye
Mirta M. L. Sousa
Gunn A. Hildrestrand
Luisa Luna
Katja Scheffler
Karine Øian Bjørås
Magnar Bjørås
Source :
International Journal of Molecular Sciences, Vol 22, Iss 12924, p 12924 (2021), International Journal of Molecular Sciences
Publication Year :
2021
Publisher :
MDPI AG, 2021.

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.

Details

Language :
English
ISSN :
16616596 and 14220067
Volume :
22
Issue :
12924
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences
Accession number :
edsair.doi.dedup.....58a768e6fac0d455d0d30d580baf368f