Oxidative Stress, Nrf2 and its role in Epilepsy

Abstract

Abstract

Epilepsy is a neurological disorder characterized by a long-lasting predisposition to generate epileptic seizures that affects millions of people around the world. The International League Against Epilepsy (ILAE) has presented an operational classification of the types of seizures depending on the etiology of the disease. A common denominator of the different types of epilepsy is the existence of imbalance of excitation and inhibition as the main mechanism of the transition from normal brain function to seizure. An imbalance between the glutamate and gamma-aminobutyric acid neurotransmitter systems can cause hyperexcitability, excitotoxicity, proliferation of reactive oxygen species and reactive nitrogen species, oxidative stress, mitochondrial damage and subsequently cell death. Oxidative stress plays a fundamental role in the mechanisms of action in the disease, since neuronal hyperexcitability plays a fundamental role in the initiation and progression of epilepsy. To avoid the damage generated by oxidative stress, cells are equipped with a variety of antioxidants that serve to counteract the effect of oxidants in which enzymatic and non-enzymatic components are involved. Enzyme compounds are regulated by Nrf2, which under oxidative stress conditions bind to antioxidant response elements and thus increases the induction of cytoprotective enzymes mediated by this factor in astrocytes and neurons. For the study of the role that oxidative stress plays in epilepsy, animal models are used that reproduce these disease conditions. This review summarizes the evidence on the role that Nrf2 plays in epilepsy by mediating the activation of antioxidant systems as cellular protectors against oxidative stress.