A focus on the roles of histones in health and diseases.

Over time, the knowledge on the role of histones has significantly changed. Initially, histones were only known as DNA packaging proteins but later, it was discovered that they act extracellularly as powerful antimicrobial agents and also as potentially self-detrimental agents. Indeed, histones were found to be the most abundant proteins within neutrophil extracellular traps what ultimately highlighted their microbicidal function. In addition, extracellular histones proved to be involved in triggering exacerbated inflammatory and coagulation responses, depending on the cell type affected. Consequently, several investigations were conducted towards studying the potential of histones and their derivatives as either biomarkers or therapeutic target candidates in different diseases in which inflammation and thrombosis have a key pathophysiological role, such as sepsis, thrombosis and different types of cancer. The main objective of this review is to summarize and discuss the current state of the art with regard to both beneficial and harmful roles of histones and also their possible use as biomarkers and therapeutic targets.