HMGB1,neuronal excitability and epilepsy

Epilepsy is a common neurological disease caused by synchronous firing of hyperexcitable neurons.Currently,antiepileptic drugs remain the main choice to control seizure,but 30%of patients are resistant to the drugs,which calls for more research on new promising targets.Neuroinflammation is closely associated with the development of epilepsy.As an important inflammatory factor,high mobility group protein B1(HMGB1)has shown elevated expression and an increased proportion of translocation from the nucleus to the cytoplasm in patients with epilepsy and in multiple animal models of epilepsy.HMGB1 can act on downstream receptors such as Toll-like receptor 4 and receptor for advanced glycation end products,thereby activating interleukin(IL)-1βand nuclear factor kappa-B(NF-κB),which in turn act with glutamate receptors such as the N-methyl-D-aspartate(NMDA)receptors to aggravate hyperexcitability and epilepsy.The hyperexcitability can in turn stimulate the expression and translocation of HMGB1.Blocking HMGB1 and its downstream signaling pathways may be a direction for antiepileptic drug therapy.Here,we review the changes of HMGB1-related pathway in epileptic brains and its role in the modulation of neuronal excitability and epileptic seizure.Furthermore,we discuss the potentials of HMGB1 as a therapeutic target for epilepsy and provide perspective on future research on the role of HMGB1 signaling in epilepsy.