Redox Biology: Specific inhibition of NADPH oxidase 2-modified chronic epilepsy

Reactive oxygen species (ROS) are important intercellular signaling molecules, and their levels depend on the activity of ROS-producing enzymes and the antioxidant capacity
of cells.
Under physiological conditions, there is a stable balance
between ROS production and antioxidant availability.
Oxidative stress (OS) occurs when ROS levels exceed cellular antioxidant defenses, which is caused by excessive ROS production or decreased cellular antioxidant capacity
.

Recent work has shown that after brain injury such as status epilepticus, NADPH oxidase (NOX) is a major producer of reactive oxygen species (ROS), contributing to neuronal damage and the development of
epilepsy.
While several NOX subtypes have been studied in the context of epilepsy, the one that has received the most attention is NOX2
.

Image source: https://doi.
org/10.
1016/j.
redox.
2022.
102549

Recently, researchers from the Hebrew University of Jerusalem published an article in the journal Redox Biology entitled "Specific inhibition of NADPH oxidase 2 modifies chronic epilepsy", the results suggest that NOX2 may play an important role in the regulation of epileptiform activity and mediate seizure-induced NOx activation.
ROS production and intracerebral oxidative stress play a key role, thus playing an important role
in the occurrence and development of epilepsy after brain injury.

In this study, the researchers demonstrated the role
of gp91ds-Tat, a specific competitive inhibitor of NOX2, in vitro epileptiform activity models and rat temporal lobe epilepsy (TLE) models.
The researchers found that in an in vitro epilepsy model, gp91ds-Tat regulates calcium oscillations and prevents epileptiform activity-induced ROS production, mitochondrial depolarization, and neuronal death
.

The administration of gp91ds-TAT 1 h after status epilepticus caused by sea human acid significantly reduced the expression and total NOX activity
of NOX2 in the cerebral cortex and hippocampus.
Finally, the researchers found that after continuous ventricle administration in epileptic rats, GP91DS-TAT significantly reduced the frequency of seizures and the total number of seizures compared to animals treated with disrupted
peptides.

Selective treatment of GP91DS-TAT inhibits the progression of epilepsy and improves chronic epilepsy

Image source: https://doi.
org/10.
1016/j.
redox.
2022.
102549

In summary, this study provides evidence for the important role of NOX2 in epilepsy, not only as the production of ROS, but also as a hint of the mechanism of anti-epilepsy, thereby significantly promoting the death of neurons after brain injury such as SE and inhibiting the development of
epilepsy.
However, the exact mechanism and molecular targets by which NOX2 regulates epileptiform activity needs further study
.
(Biovalley Bioon.
com)

References

Prince Kumar Singh et al.
Specific inhibition of NADPH oxidase 2 modifies chronic epilepsy.
Redox Biol.
2022 Dec; 58:102549.
doi: 10.
1016/j.
redox.
2022.
102549.