How is the P2X7 receptor signaling pathway involved in epileptogenesis?

Epilepsy, a condition characterized by spontaneous recurrent epileptic seizures, is among the most prevalent neurological disorders. This disorder is estimated to affect approximately 70 million people worldwide. Although antiseizure medications are considered the first-line treatments for epilepsy, most of the available antiepileptic drugs are not effective in nearly one-third of patients. This calls for the development of more effective drugs. Evidence from animal models and epilepsy patients suggests that strategies that interfere with the P2X7 receptor by binding to adenosine triphosphate (ATP) are potential treatments for this patient population. This review describes the role of the P2X7 receptor signaling pathways in epileptogenesis. We highlight the genes, purinergic signaling, Pannexin1, glutamatergic signaling, adenosine kinase, calcium signaling, and inflammatory response factors involved in the process, and conclude with a synopsis of these key connections. By unraveling the intricate interplay between P2X7 receptors and epileptogenesis, this review provides ideas for designing potent clinical therapies that will revolutionize both prevention and treatment for epileptic patients. •The role of the P2X7R signaling pathways in epileptogenesis.•The genes, purinergic signaling, pannexin1, glutamatergic signaling, adenosine kinase, calcium signaling, and inflammatory response factors involved in epileptogenesis.•The controversy over P2X7R's cellular specificity in the nervous system and its contradictory activities in different epilepsy models.