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

Abstract

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.

Severe Acute Respiratory Syndrome Coronavirus 2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

“…Indeed, reduced activity of the Ang (1–7)/MasR pathway would decrease the antioxidant and anti-inflammatory mediators in the brain parenchyma (Figure 3). In fact, brain RAS has been involved in seizures and epilepsy where hyperactivation of Ang II/ATR1 signaling in astrocytes and microglia have been observed (Krasniqi and Daci, 2019). Reduced brain blood flow and ischemia are other known consequences of altered RAS activity and could also be the result of reduced endothelial ACE2 expression caused by the SARS-CoV-2 infection (reviewed in Najjar et al., 2020).…”

Hearing Loss in SARS-CoV-2: What Do We Know?

“…Severe acute respiratory syndrome coronavirus 2 attaches to the hemoglobin via β chain, gaining entry into erythrocytes, which acts as a transporter ergo, infecting all tissues by binding to the surface receptor, angiotensin-converting enzyme 2 (ACE2). As ACE2 has been reported to be abundant in the brain, medulla oblongata, 4 and temporal lobe, the hearing center becomes affected, paving the way to hearing loss. Severe acute respiratory syndrome coronavirus 2 causes cytokine release once it binds to the surface receptor, ACE2.…”

Comment on “Hearing loss and COVID-19: A note”

“…The virus can be transported with erythrocytes or vascular endothelium, possibly infecting all tissues with ACE2 in its structure. There are plenty of ACE2 in the brain and medulla oblongata [5]. The hearing center is in the temporal lobe of the brain.…”

“…It is also ACE2 here. ACE2 overexpression in the brain, except medulla oblongata, has a positive effect such as anti-inflammatory antioxidant and blood pressure regulator [5]. However, if cytosolic pH is low, an increase in ACE2 causes an increase in viral load [2,3].…”