The neuroinflammatory astrocytic P2X7 receptor: Alzheimer's disease, ischemic brain injury, and epileptic state

Abstract

Introduction: Astrocytes have previously been considered as cells supporting neuronal functions, but they are now recognized as active players in maintaining central nervous system (CNS) homeostasis. Astrocytes can communicate with other CNS cells, i.e. through the gliotransmitter ATP and P2X7 receptors (Rs).

Areas covered: In this review, we will discuss how the P2X7R initiates the release of gliotransmitters and proinflammatory cytokines/chemokines, thereby establishing a dialog between astrocytes and neurons and, in addition, causing neuroinflammation. In astrocytes, dysregulation of P2X7Rs has been associated with neurodegenerative illnesses such as Alzheimer's disease (AD), as well as the consequences of cerebral ischemic injury and status epilepticus (SE).

Expert opinion: Although all CNS cells are possible sources of ATP release, the targets of this ATP are primarily at microglial cells. However, astrocytes also contain ATP-sensitive P2X7Rs and have in addition the peculiar property over microglia to continuously interact with neurons via not only inflammatory mediators but also gliotransmitters, such as adenosine 5'-triphosphate (ATP), glutamate, γ-amino butyric acid (GABA), and D-serine. Cellular damage arising during AD, cerebral ischemia, and SE via P2X7R activation is superimposed upon the original disease, and their prevention by blood-brain barrier permeable pharmacological antagonists is a valid therapeutic option.

Keywords: Alzheimer’s disease; P2X7 receptor antagonists; P2X7 receptors; apoptosis; ischemic stroke; necrosis; neurodegenerative illnesses; status epilepticus.