The roles of ER stress in epilepsy: Molecular mechanisms and therapeutic implications

[Display omitted] •Dysregulated ER stress and UPR may be implicated in the pathogenesis of epilepsy.•Interventions targeting ER stress have exerted antiepileptic and neuroprotective effects.•Therapeutic approaches targeting ER stress may open a new scenario for antiepileptic treatments. Epilepsies are a diverse group of neurological disorders, which are characterized by spontaneous recurrent seizures. Although a wide range of pathogenic mechanisms such as alterations in ion channels, inflammation and neuronal loss have been reported to be implicated in the epileptogenesis, the underlying pathogenesis of epilepsy remains unclear currently. Endoplasmic reticulum (ER) stress is regarded as a condition that unfolded or misfolded proteins accumulate in the ER lumen. Excessive or prolonged ER stress causes the activation of the unfolded protein response (UPR) to buffer ER stress and restore ER homeostasis. Increasing evidence has indicated dysregulated ER stress during epileptogenesis, which may participate in various pathological processes associated with epilepsy. In this present review, we summarized recent advances in the involvement of ER stress in the pathogenesis of epilepsy. Additionally, the antiepileptic and neuroprotective effects of interventions targeting ER stress were also discussed.