The Role of Extracellular Histones in Disease Progression: A Potential Therapeutic Target for Disease Modulation

Histones were once thought to be exclusive to the nucleus, but were recently discovered in the extracellular space, where they play important roles in disease pathogenesis. In addition to their traditional functions in chromatin organization and gene regulation, extracellular histones also serve as damage-associated molecular patterns (DAMPs), drive inflammation and immune responses, and are responsible for the progression of diseases such as sepsis, autoimmune diseases, and inflammatory diseases. To effectively target extracellular histones and improve disease progression, this review begins with the release and pathogenic mechanisms of histones and explains the main pathogenic mechanisms of extracellular histones in many diseases. In addition, common antagonistic methods for targeting extracellular histones are summarized, and the mechanisms that need to be further studied at this stage are discussed, providing new directions for the future development of effective and safe histone-targeting drugs.