Free radical induced oxidative damage to DNA: relation to brain aging and neurological disorders.

ABSTRACT

Free radicals are produced in cells by cellular metabolism and by exogenous agents. These species react with biomolecules in cells and one of the important targets is DNA. This kind of damage, often referred to as oxidative DNA damage, has consequences in various organs and particularly in brain, in view of its high metabolic activity and oxygen consumption. The consequences include mutagenesis of various kinds ranging from simple oxidation of bases to large deletions through single and double strand breaks. In brain, because of its post-mitotic nature, oxidative damage to DNA is seen more often at the level of bases. A major route for repairing oxidative damage to bases is base excision repair (BER). It is increasingly becoming apparent that defects in repairing oxidative DNA damage can lead to a number of neurological disorders like Alzheimer and Parkinson. Our recent studies have clearly demonstrated that BER is highly compromised in brain cells with increasing age and this could well be one of the major causative factors for normal aging and the associated deteriorating mental conditions, including certain neurological abnormalities.