Role of the Angiotensin Pathway and its Target Therapy in Epilepsy Management

Despite extensive research on epileptogenesis, there is still a need to investigate new pathways and targeted therapeutic approaches in this complex process. Inflammation, oxidative stress, neurotoxicity, neural cell death, gliosis, and blood⁻brain barrier (BBB) dysfunction are the most common causes of epileptogenesis. Moreover, the renin⁻angiotensin system (RAS) affects the brain's physiological and pathological conditions, including epilepsy and its consequences. While there are a variety of available pharmacotherapeutic approaches, information on new pathways is in high demand and the achievement of treatment goals is greatly desired. Therefore, targeting the RAS presents an interesting opportunity to better understand this process. This has been supported by preclinical studies, primarily based on RAS enzyme, receptor-inhibition, and selective agonists, which are characterized by pleiotropic properties. Although there are some antiepileptic drugs (AEDs) that interfere with RAS, the main targeted therapy of this pathway contributes in synergy with AEDs. However, the RAS-targeted treatment alone, or in combination with AEDs, requires clinical studies to contribute to, and clarify, the evidence on epilepsy management. There is also a genetic association between RAS and epilepsy, and an involvement of pharmacogenetics in RAS, so there are possibilities for the development of new diagnostic and personalized treatments for epilepsy.