The role of HMGB-1 and its inhibitors in brain disorders

High Mobility Group Box-1 (HMGB-1) plays a crucial role in several physiological and pathological processes in the body depending on its localization, post-translational modification status, the environment of the compartment it occupies, and essential for life. In the basal state, HMGB-1 is concentrated 30-fold in the nucleus compared to the cytoplasm, but depending on the environment and stimulus, it can be localized to the cytoplasm, cell membrane, and extracellular compartments. Its most studied and well-known receptors are Receptor for Advanced Glycation End-products (RAGE) and Toll-like Receptors (TLR), specifically TLR4. HMGB-1 can bind to RAGE and TLR4 and act upon cell differentiation, migration, and, most importantly, inflammation. This chapter aims to summarize new data on the experimental and clinical research of HMGB1, and its current inhibitors in brain disorders, specifically epilepsy, headache, neuroimmunological disorders, neurodegenerative disorders, and stroke.