The Potential Therapeutic Role of the HMGB1-TLR Pathway in Epilepsy

Epilepsy is one of the most common serious neurological disorders, affecting over 70 million people worldwide. For the treatment of epilepsy, antiepileptic drugs (AEDs) and surgeries are widely used. However, drug resistance and adverse effects indicate the need to develop targeted AEDs based on further exploration of the epileptogenic mechanism. Currently, many efforts have been made to elucidate the neuroinflammation theory in epileptogenesis, which may show potential in the treatment of epilepsy. In this respect, an important target protein, high mobility group box 1 (HMGB1), has received increased attention and has been developed rapidly. HMGB1 is expressed in various eukaryotic cells and localized in the cell nucleus. When HMGB1 is released by injuries or diseases, it participates in inflammation. Recent studies suggest that HMGB1 via Toll-like receptor (TLR) pathways can trigger inflammatory responses and play an important role in epilepsy. In addition, studies of HMGB1 have shown its potential in the treatment of epilepsy. Herein, the authors analyzed the experimental and clinical evidence of the HMGB1-TLR pathway in epilepsy to summarize the theory of epileptogenesis and provide insights into antiepileptic therapy in this novel field.