GPR40 and Postsynaptic NMDA Receptors: A Pair Against Epilepsy

Epilepsy is a chronic neurological condition characterized by abnormal brain activity, unusual behavior, and loss of awareness. One of the most common features is the spontaneous recurrence of unprovoked seizures that mainly affect the hippocampus and cortical regions of the brain. Although the exact cause of epilepsy is still unknown, a mix of genetic, neurological, and environmental factors play a role. A novel study by Yang et al. explores the metabotropic receptor GPR40 which is suspected to be involved in the regulation of epileptic seizures, specifically through its modulatory role on NMDA receptors in the central nervous system. Their findings suggest that GPR40 induces NMDA receptor endocytosis via direct interaction with NR2A and NR2B subunits of postsynaptic NMDA receptors. Through this mechanism, NMDA-mediated postsynaptic currents are altered, resulting in reduced seizure-like activity. This review article discusses these novel findings which not only shed light on the potential molecular mechanisms of epilepsy but also push the scientific community closer to developing a treatment for this disorder.