A Central Role for ATP Signalling in Glial Interactions in the CNS

Title:A Central Role for ATP Signalling in Glial Interactions in the CNS

Volume: 17 Issue: 16

Author(s): Andrea Rivera, Ilaria Vanzulli and Arthur M. Butt

Affiliation:

Keywords: Glia, astrocyte, oligodendrocytes, ATP, purine receptor.

Abstract: The purine ATP has a prominent regulatory role in CNS function and pathology due to its actions on glial cells - microglia, astrocytes and oligodendrocytes. ATP serves as an apparently ubiquitous ‘gliotransmitter’ that is released by astrocytes and other cells to activate purine receptors on neighbouring cells. In pathology, the release of ATP mediates both tissue damage and repair by its direct effects on glial cell integrity and survival. The actions of ATP on glia are mediated via a wide range of receptors, broadly divided into ionotropic P2X and metabotropic (G-protein coupled receptors (GPCR)) P2Y receptors, of which there are multiple subtypes (P2X₁-P2X₇ and P2Y₁-P2Y₁₄). ATP-mediated interactions between astrocytes and microglia are at the centre of immune responses in the CNS, with prominent roles for the P2X₄, P2X₇, P2Y₁, P2Y₆ and P2Y₁₂ receptor subtypes. In oligodendrocytes, P2X₇ and P2Y₁ receptor subtypes have a bipartite function in respectively mediating oligodendrocyte destruction and protection. Purine receptors mediate glial pathology, with prominent roles in ischemia, neuroinflammation, Multiple Scelerosis, neuropathic pain and traumatic injury. Notably, glial ATP signalling may be altered with ageing and is implicated in impaired myelination and immunity in Alzheimer’s disease. Hence, glial purine receptors provide potential therapeutic targets in multiple neuropathologies, but the ‘Jeckyll and Hyde’ nature of purine signalling underscores the importance of further research and a comprehensive understanding of the roles of the different purine receptors in mediating tissue damage and repair.

Cite this article as:

Rivera Andrea, Vanzulli Ilaria and Butt M. Arthur, A Central Role for ATP Signalling in Glial Interactions in the CNS, Current Drug Targets 2016; 17 (16) . https://dx.doi.org/10.2174/1389450117666160711154529