HMGB1: a double-edged sword and therapeutic target in the female reproductive system

Abstract

HMGB1 that belongs to the High Mobility Group-box superfamily, is a nonhistone chromatin associated transcription factor. It is present in the nucleus of eukaryotes and can be actively secreted or passively released by kinds of cells. HMGB1 is important for maintaining DNA structure by binding to DNA and histones, protecting it from damage. It also regulates the interaction between histones and DNA, affecting chromatin packaging, and can influence gene expression by promoting nucleosome sliding. And as a DAMP, HMGB1 binding to RAGE and TLRs activates NF-κB, which triggers the expression of downstream genes like IL-18, IL-1β, and TNF-α. HMGB1 is known to be involved in numerous physiological and pathological processes. Recent studies have demonstrated the significance of HMGB1 as DAMPs in the female reproductive system. These findings have shed light on the potential role of HMGB1 in the pathogenesis of diseases in female reproductive system and the possibilities of HMGB1-targeted therapies for treating them. Such therapies can help reduce inflammation and metabolic dysfunction and alleviate the symptoms of reproductive system diseases. Overall, the identification of HMGB1 as a key player in disease of the female reproductive system represents a significant breakthrough in our understanding of these conditions and presents exciting opportunities for the development of novel therapies.

The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

“…DAMPs serve as ubiquitous "warning signals" released from damaged or deceased cells, including neurons and glial cells within the brain [127]. One prominent DAMP in neuroinflammation is the high mobility group protein, HMGB1 [128]. In a study utilizing ischemia-reperfusion injury as a model, it was observed that IRI led to an increase in HMGB1 expression and upregulation of NF-κB p65 in brain tissue.…”