Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER-R), Lucknow, UP, 226002, India.
Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research-Raebareli (NIPER-R), Lucknow, UP, 226002, India.
Mol Neurobiol. 2023 Jul;60(7):3600-3616. doi: 10.1007/s12035-023-03289-9. Epub 2023 Mar 2.
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.
神经炎症是神经退行性变的主要影响因素。这是一个复杂的过程，始于细胞损伤触发先天免疫系统，导致损伤相关分子模式（DAMPs）的产生，这些模式也被认为是内源性危险标志物。这些源自细胞在病理刺激下的各个隔室。这些是非常流行的候选物，它们起源于细胞的细胞内隔室和细胞器，并且其作用部位本身可能在细胞内或细胞外空间。在病理刺激的影响下，它们与模式识别受体相互作用，启动促炎级联反应，随后释放细胞因子。这为诊断和治疗干预提供了一个很好的机会，为修复和逆转创造了更好的条件。由于主要的贡献者来自细胞内隔室，因此在本综述中，我们试图重点关注来自细胞内隔室的 DAMPs 分子及其在神经退行性事件中的特定作用，解释它们的下游介质和信号。此外，我们还试图涵盖 DAMPs 作为临床生物标志物的最新干预措施，这些标志物可以帮助检测疾病，还可以靶向它以减少先天免疫激活反应，从而有助于减少在神经退行性过程中具有整体作用的无菌性神经炎症。
