Beschreibung:
P2X7 receptors are ion-gated channels activated by ATP. Under pathological conditions,the extensive release of ATP induces sustained P2X7 receptor activation, culminatingin induction of proinflammatory pathways with inflammasome assembly and cytokinerelease. These inflammatory conditions, whether occurring peripherally or in the centralnervous system (CNS), increase blood-brain-barrier (BBB) permeability. Besides its well-known involvement in neurodegeneration and neuroinflammation, the P2X7 receptormay induce BBB disruption and chemotaxis of peripheral immune cells to the CNS,resulting in brain parenchyma infiltration. For instance, despite common effects oncytokine release, P2X7 receptor signaling is also associated with metalloproteinasesecretion and activation, as well as migration and differentiation of T lymphocytes,monocytes and dendritic cells. Here we highlight that peripheral immune cells mediatethe pathogenesis of Multiple Sclerosis and Parkinson’s and Alzheimer’s disease, mainlythrough T lymphocyte, neutrophil and monocyte infiltration. We propose that P2X7receptor activation contributes to neurodegenerative disease progression beyond itsknown effects on the CNS. This review discusses how P2X7 receptor activationmediates responses of peripheral immune cells within the inflamed CNS, as occurringin the aforementioned diseases.