Epochal neuroinflammatory role of high mobility group box 1 in central nervous system diseases

摘要

The central nervous system (CNS) is enriched with a developed reaction reserve dubbed “neuroinflammation”, which facilitates it to cope with pathogens, toxins, traumata and degeneration. Inflammation is a significant biological activity in reaction to injury, infection, and trauma agonized by cells or tissues. A positive inflammatory reaction mechanism removes attacking pathogens, initiating wound healing and angiogenesis. The High Mobility Group Box 1 (HMGB1) protein is abundant and ubiquitous nuclear proteins that bind to DNA, nucleosome and other multi-protein complexes in a dynamic and reversible fashion to regulate DNA processing in the context of chromatin. Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. HMGB1 protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors such as cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. With regards to these various disease condition above, our review focus on the role of HMGB1 and CNS Diseases.