Innate signals of cellular stress

Innate signals of cellular stress refers to a broad category of endogenous molecules, often termed Damage-Associated Molecular Patterns (DAMPs) or alarmins, that are released or exposed by cells undergoing injury, metabolic stress, or non-programmed death. These signals are recognized by the innate immune system through various pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and the cGAS-STING pathway, to initiate an inflammatory response and promote tissue repair. While not a single therapeutic target itself, the pathways and molecules involved in sensing these stress signals—such as the NLRP3 inflammasome or the Integrated Stress Response (ISR)—are major areas of drug development for treating inflammatory, autoimmune, and neurodegenerative diseases. Dysregulation of these signals is implicated in sterile inflammation, which contributes to the pathogenesis of conditions like atherosclerosis, Alzheimer's disease, and cancer. Therapeutic interventions typically target the sensors or downstream effectors of these signals rather than the signals themselves, which are often diverse and transient. Monitoring these signals, such as HMGB1 or cell-free DNA, provides valuable biomarkers for disease activity and treatment response.

Other names

Damage-associated molecular patternsDAMPsAlarminsEndogenous danger signalsSterile inflammation signalsCellular stress signals

Modulation of pattern recognition receptors (PRRs) or stress-response kinases that detect endogenous signals of cellular damage.