Intracellular DAMPs in Neurodegeneration and Their Role in Clinical Therapeutics

Neuroinflammation is the major implication of neurodegeneration. This is a complex process which initiates from the cellular injury triggering the innate immune system which gives rise to damage-associated molecular patterns (DAMPs) which are also recognized as endogenous danger indicators. These originate from various compartments of the cell under pathological stimulus. These are very popular candidates having their origin in the intracellular compartments and organelles of the cell and may have their site of action itself in the intracellular or at the extracellular spaces. Under the influence of the pathological stimuli, they interact with the pattern-recognition receptor to initiate their pro-inflammatory cascade followed by the cytokine release. This provides a good opportunity for diagnostic and therapeutic interventions creating better conditions for repair and reversal. Since the major contributors arise from the intracellular compartment, in this review, we have attempted to focus on the DAMP molecules arising from the intracellular compartments and their specific roles in the neurodegenerative events explaining their downstream mediators and signaling. Moreover, we have tried to cover the latest interventions in terms of DAMPs as clinical biomarkers which can assist in detecting the disease and also target it to reduce the innate-immune activation response which can help in reducing the sterile neuroinflammation having an integral role in the neurodegenerative processes.

Automated summary

Neuroinflammation, triggered by cellular injury and the innate immune system, is a critical factor in neurodegenerative diseases. Damage-associated molecular patterns (DAMPs) are endogenous danger indicators released from different compartments of cells under pathological stimulation, and they play a significant role in the inflammatory cascade and cytokine release. This review focuses on DAMP molecules originating from intracellular compartments and their roles in neurodegenerative events, including downstream mediators and signaling pathways. Additionally, recent interventions involving DAMPs as clinical biomarkers for disease detection and targeting the innate immune activation response to reduce sterile neuroinflammation are discussed.