Targeting crosstalk between Nuclear factor (erythroid-derived 2)-like 2 and Nuclear factor kappa beta pathway by Nrf2 activator dimethyl fumarate in epileptogenesis

ABSTRACT

Purpose/Aim: Epilepsy is a complex, chronic neurological disorder characterized by increased and abnormal synchronization of neuronal electrical activity, which is manifested as seizures. It is associated with many comorbid conditions such as depression, anxiety, sleep disorder, psychiatric disorder etc., which consequently causes higher mortality rate. The understanding of its cellular and molecular mechanism is partial, because of which it remains an ongoing health problem, despite the increasing availability of newer antiepileptic drugs. Although recurrent seizures are the clinical indication of epilepsy, the disease process (epileptogenesis) begins before the onset of the first seizure. This dormant phase before the onset of first seizure provides an opportune time window for modifying the epileptogenic process by intervening in its progression with an appropriate treatment. Material and Methods: Studies have shown that in epilepsy, there is a chronic state of oxidative stress and inflammation, which plays a key role in epileptic pathogenesis. Various antioxidant mechanisms maintain the redox balance in the body by either scavenging or regulating the generation of free radicals. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway is a well-established antioxidant pathway in various diseases such as diabetes, renal disease, various neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, etc. Results: It has been observed that single-target therapies are inefficient in providing anticonvulsant and disease-modifying effects in epilepsy. Conclusions: So, preventing the progression of epilepsy by targeting Nrf2-activated antioxidant pathway along with the other established antiepileptic pathways can prove beneficial in epilepsy treatment.

KEYWORDS:

• Epileptogenesis
• Nrf2
• NF-кB
• dimethyl fumarate (DMF)
• oxidative stress

Acknowledgments

We thank Ms. Puja Kumari (PhD scholar) for useful discussion.

Disclosure statement

No potential conflict of interest was reported by the authors.