Neurotoxicant-Induced Oxidative Events and Antioxidative Interventions in the Central Nervous System
Exposure to some environmental neurotoxicants produces an increased concentration of reactive oxygen species (ROS) in the brain. These reactive molecules form macromolecular adducts, subsequently deplete the cell of endogenous antioxidative factors, and precipitate oxidative injury in the central nervous system (CNS). However, this mechanism of action is not limited to neurotoxicants exposure. In fact, oxidative injury is common in the etiology and progression of neurodegenerative disease as well. A reduction in the intracellular ROS through the use of direct antioxidants is one strategy used in the clinical management of neurodegeneration and may also be beneficial in response to acute and chronic exposure to neurotoxicants. Alternatively, indirect antioxidative therapy might be achieved through the enhancement of expression of antioxidative genes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an inducible transcription factor that controls the expression of a battery of such genes. Animal models provide evidence that the induction of the Nrf2 pathway is protective against multiple models of oxidative damage in the CNS. Activation of Nrf2 shows promise as a neurotherapeutic and may be a useful pharmacological target in future studies in humans with CNS oxidative damage.
