DAMPs : The trigger molecules of persistent inflammation

Damage-associated molecular Patterns (DAMPs) are endogenous molecules released on the onset of tissue injury, which activate various innate signalling cascades through pattern recognition receptors (PRRs). DAMPs are released due to stress, external stimuli, and cell death. They have been reported to play a crucial role in various disease conditions such as autoimmune disorders, cancer, chronic kidney disease, diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). Crucial DAMPs, such as HMGB1, HSP90, S100 proteins, and ATP, tend to exert their inflammatory activity primarily through cell surface receptors, including TLR4, RAGE, CD36, P2X7, and P2Y2. The DAMPs often activate NF-κB, MAPK, and NLRP3 inflammasome formation, further increasing the inflammation via positive feedback. In the past decades, various inhibitors of DAMPs and interacting receptors have been developed, which have to be evaluated for their safety and efficacy. Further, the various signalling mechanism of the DAMPs contributing to its inflammatory function needs to be elucidated. However, DAMPs inevitably remain as a potent mediator of persistent inflammation that needs to be addressed for developing therapeutics to overcome the catastrophic effects of DAMP molecules.