Abstract
Recent evidence indicates that the occurrence of psychiatric disorders in patients is linked to a local “sterile” inflammation of brain or due to a systemic inflammation process that affects the central nervous system. This is supported by the observation that in peripheral blood of psychotic patients are detectable several mediators and markers of inflammation as well as clinical data on correlations between systemic chronic inflammatory processes and psychiatric disorders. This may explain why some reported anti-inflammatory treatment strategies have beneficial effects on ameliorating psychotic events. In this review we will present a concept that aberrant purinergic signaling and increases in extracellular level of adenosine triphosphate (ATP) in the brain parenchyma may lead to activation of Nlrp3 inflammasome in microglia cells and as a consequence microglia released danger associated molecular pattern (DAMP) proteins activate complement cascade (ComC) in mannan binding lectin (MBL) – dependent manner. Activation of ATP-Nlrp3 inflammasome-ComC axis may also orchestrate trafficking of stem cells released from bone marrow into peripheral blood observed in psychotic patients. Based on this, the ATP-Nlrp3 inflammasome-ComC axis may become a target for new therapeutic approaches, which justifies the development and clinical application of efficient anti-inflammatory treatment strategies targeting this axis in psychiatry.
Highlights
Mental or psychiatric disorders remain a significant global health problem
We propose that extracellular adenosine triphosphate (ATP)-Nlrp3 inflammasome-complement cascade (ComC) axis is a driver of sterile inflammation in the brain leading to psychotic disorders
Extracellular ATP activated Nlrp3 inflammasome plays an important role as a gear or cogwheel between purinergic signaling and ComC [16]
Summary
Mental or psychiatric disorders remain a significant global health problem. According to World Health Organization. Microglia belong to glial system of non-neuronal cells and their relationship to cellular arm of innate immunity has been discussed earlier in this review They account for 5– 20% of all glia cell population in central nervous system parenchyma and play an important role in brain development by regulating proliferation and differentiation of neural cells as well as are involved in the formation of synaptic connection by phagocytic removal of redundant or less effective in signaling synapses [14, 19]. To support this notion activation of Nlrp inflammasome has been already demonstrated to be involved in major mental disorders [15]. ATP-P2X7 interaction activates intracellular enzyme caspase 1 that promotes by proteolytic
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