High Mobility Group Box-1 (HMGB1) And Its Possible Correlation With Epilepsy Among Children

Abstract

Background: Cytokines are proteins that range in size from 3,000– 70,000 Kilo Dalton and function as principal mediators of cellular communication and coordination of cellular activities. They can function in a manner that is intracrine (acting within a cell), autocrine (secreted and acting on the same cell), paracrine (signalling to adjacent cells) or endocrine (acting distantly through the blood), in responses to danger, damage or injury. HMGB1 is a nonhistone nuclear protein that is loosely bound to chromatin. It is present in almost all eukaryotic cells. HMGB1 plays important roles in the stabilization of nucleosome formation, DNA repair in nuclei, and act as a transcription factor-like protein that regulates the expression of several genes.  Recently, it is known that HMGB1 is also secreted by mature dendritic cells (DCs), activated macrophages, and natural killer (NK) cells in response to infection, injury, or other inflammatory stimuli. In this way, HMGB1 is one of the main prototypes of the emerging Damage-Associated Molecular Pattern Molecules (DAMPs). High mobility group box1 protein (HMGB1), which is encoded on human chromosome 13q, is a nuclear-binding protein. It is a cytokine-like factor that is released from necrotic cells and secreted by activated macrophages. As a cytokine, HMGB1 activates endothelial cells, promotes angiogenesis, enhances hematopoietic stem-cell migration and initiates inflammation. Inflammation-induced via several brain-disrupting events such as trauma, stroke, and infection are associated with epileptic seizures. HMGB1 is one of the most influential pro-inflammatory cytokines and activates inflammatory pathways by stimulating two principal receptors: RAGE and TLR4, and activation of these receptors have been implicated in epileptogenesis. Understanding the dynamics of HMGB1 translocation and activity is an important factor that will be helpful in assessing the disease pathology. the release of HMGB1 from nuclei in a range of neurological disorders including epilepsy. The nuclear to cytosol translocation of HMGB1 and its release from neural cells is associated with post-translational modifications and is implicated in the epileptic seizure generation with the interaction with RAGE or TLR4.