Damage-associated molecular pattern molecule (DAMP)

Damage-associated molecular pattern molecules (DAMPs) are a diverse set of endogenous molecules released by stressed, damaged, or dying cells that signal tissue injury or danger to the body[1][2][3][5]. Rather than a unique protein or receptor, DAMPs comprise nuclear, cytosolic, membrane, and extracellular matrix components—including proteins (HMGB1, S100, histones), ATP, uric acid, DNA/RNA fragments, ECM breakdown products, and others[1][2]. Upon release, these molecules activate innate immune responses by binding to pattern recognition receptors (PRRs) such as toll-like receptors (TLRs), NOD-like receptors (NLRs), and receptor for advanced glycation end products (RAGE)[1][2]. This triggers inflammation, recruitment of immune cells, and initiation of tissue repair, but can also perpetuate chronic inflammation and contribute to pathology in a range of diseases (e.g., sepsis, cancer, autoimmune disorders, neurodegeneration, acute organ injury)[1][2][3][5]. Individual DAMPs are being studied as disease biomarkers and drug targets, but the class itself describes a functional role rather than a single molecular entity. Most commonly, research refers to particular DAMPs (e.g., HMGB1, S100 proteins, ATP, uric acid) or their downstream signaling receptors (e.g., TLR4, RAGE, NLRP3)[1][2][3]. Drug development focuses on these specific targets, not "DAMPs" as an undifferentiated group. The term is best used for describing a biological mechanism or classification, not for designating a therapeutic target molecule[1][2][3][5].

Other names

DAMPalarmindanger signal

Inhibition of PRR signaling (e.g., preventing DAMPs from binding TLRs/RAGE), suppression of downstream inflammation (e.g., NF-κB pathway), or neutralization of specific DAMPs (e.g., anti-HMGB1 antibody)