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