Danger-associated molecular pattern (DAMP)

Danger-associated molecular patterns (DAMPs), also known as damage-associated molecular patterns or alarmins, are endogenous molecules normally hidden from immune surveillance but released or exposed by stressed, injured, or dying cells. DAMPs include a diverse array of nuclear, cytoplasmic, and extracellular matrix components, such as high-mobility group box 1 protein (HMGB1), S100 proteins, heat shock proteins, uric acid, and extracellular ATP. Once released, DAMPs trigger inflammation by binding to pattern recognition receptors (PRRs) on innate immune cells, notably TLRs, NLRs, and RAGE. This interaction can lead to beneficial tissue repair but, if dysregulated, underlies numerous pathological inflammatory responses and chronic diseases. DAMPs do not refer to a single molecule or protein receptor but rather to a molecular pattern—a classification for endogenous molecules that serve an immunological alarm function in response to non-infectious injury or cell stress. While the signaling pathways activated by DAMPs (through TLRs, NLRs, RAGE etc.) are considered therapeutic targets, DAMPs themselves as a group are not considered a therapeutic target in the conventional sense. For structured drug target databases, DAMPs should not be included as a single target entry, but rather, individual DAMP molecules (e.g., HMGB1, S100A8, ATP, etc.), or their receptors (e.g., TLR4, RAGE) should be specified as therapeutic targets. DAMPs as a category lack the specificity required for most target-based drug discovery efforts.

Other names

Damage-associated molecular patternEndogenous danger signalAlarmin