The contribution of fibronectin in epileptogenesis: therapeutic potential and mechanistic complexity.

Abstract

Introduction: Epilepsy is a chronic neurological disorder leading to repeateduncontrollable seizures. The available armamentarium of ~ 30 antiseizure drugsis unable to control seizures in a third of the patients, which signifies the need to look for novel therapeutic targets with alternative mechanisms of action.

Areas covered: Fibronectin, an extracellular matrix (ECM) glycoprotein,is involved in epileptogenesis as shown by several clinical and preclinicalstudies. There is ample evidence supporting fibronectin's role in modulatingkey pathognomonic events during epileptogenesis. This review presents a conciseoverview of fibronectin's contribution to the initiation and progression ofepilepsy. Additionally, we highlight the potential of fibronectin to betargeted for developing novel anti-epileptogenic therapeutics.

Expert opinion: Epileptogenesis involves aberrant angiogenesis,blood-brain barrier (BBB) perturbation, neuroinflammation, synaptic remodeling,and neuronal hyperexcitability, all of which are significantly regulated byfibronectin. Small-molecule inhibitors against fibronectin could disrupt the signaling pathways that influence hyperexcitability, BBB disruption, andaberrant neurogenesis during epileptogenesis. Alternatively, delivering fibronectin/nanomedicine complex to the brain could help target neuroinflammation, as demonstrated in other diseases. However, current evidence supporting fibronectin as a therapeutic target in epilepsy remains limited,highlighting the need for further research to better understand its role in epileptogenesis.