Abstract
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.
Highlights
Inflammation is a reaction to the innate immune system that is initiated by infection or injury
Researchers have developed interest in exploring of the role of High Mobility Group Box 1 (HMGB1) in the central nervous system (CNS) very recently and HMGB1 has been studied extensively in patients affected with autistic disorders, anorexia nervosa, traumatic brain injury (TBI) in which HMGB1 levels are increased in cerebrospinal fluid (CSF), cell necrosis, bacterial and aseptic meningitis, epilepsy and febrile seizures where HMGB1 and proinflammatory cytokines (PIC) play a crucial pathogenic role
Studies have indicated that HMGBI acts as an important biosensor of nucleic acid inside the cells and DNA or RNA derived from viruses, bacteria, or damaged cells trigger innate immune responses through HMGB1 which is required for subsequent recognition by specific pattern receptors [45]
Summary
Inflammation is a reaction to the innate immune system that is initiated by infection or injury. It has been indicated that over secretion of HMGB1 in cardiac tissue by transgenic methods significantly increases survival and protects mice against myocardial infarction by enhancing angiogenesis and cardiac function [9]. It is indicated that HMGB1 conditional knockout strategies may cause substantially different functional phenotypes in the liver and heart [13]. Researchers have developed interest in exploring of the role of HMGB1 in the CNS very recently and HMGB1 has been studied extensively in patients affected with autistic disorders, anorexia nervosa, traumatic brain injury (TBI) in which HMGB1 levels are increased in cerebrospinal fluid (CSF), cell necrosis, bacterial and aseptic meningitis, epilepsy and febrile seizures where HMGB1 and proinflammatory cytokines (PIC) play a crucial pathogenic role. Current studies have demonstrated the role of HMGB1 as a PIC with activity in the CNS. We review the cogent role of HMGB1 in these diseases and its therapeutic potentials as well as its PIC activities in the brain
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