Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

• Published in: Neuropharmacology Vol. 104; pp. 94 - 104
• Main Authors: Beamer, Edward, Gölöncsér, Flóra, Horváth, Gergely, Bekő, Katinka, Otrokocsi, Lilla, Koványi, Bence, Sperlágh, Beáta
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-05-2016
• Subjects: Adenosine - metabolism; Adenosine Triphosphate - metabolism; Animals; Cytokines; Encephalitis - congenital; Encephalitis - metabolism; Humans; Inflammasomes - metabolism; Inflammation Mediators; Neuroinflammation; NLRP3 inflammasome; P1 receptor; P2X receptor; P2Y receptor; Receptor Cross-Talk; Receptors, Purinergic P1 - metabolism; Receptors, Purinergic P2 - metabolism; Signal Transduction; MPC; BD; MCP-1; BBB; ALS; CNS; NLRP3 inflammasome; MDD; LPS; DAMPs; ASC; sIL-2R; P2Y receptor; sIL-6R; NLRP; PAMPs; sTNFR1; SM; AD; Panx1; Cytokines; FST; PKA; Neuroinflammation; PKC; P2X receptor; MAPK; PI3K kinase; OCD; PD; TNF-α; TST; P1 receptor; TLRs
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2015.09.019

The principle functions of neuroinflammation are to limit tissue damage and promote tissue repair in response to pathogens or injury. While neuroinflammation has utility, pathophysiological inflammatory responses, to some extent, underlie almost all neuropathology. Understanding the mechanisms that control the three stages of inflammation (initiation, propagation and resolution) is therefore of critical importance for developing treatments for diseases of the central nervous system. The purinergic signaling system, involving adenosine, ATP and other purines, plus a host of P1 and P2 receptor subtypes, controls inflammatory responses in complex ways. Activation of the inflammasome, leading to release of pro-inflammatory cytokines, activation and migration of microglia and altered astroglial function are key regulators of the neuroinflammatory response. Here, we review the role of P1 and P2 receptors in mediating these processes and examine their contribution to disorders of the nervous system. Firstly, we give an overview of the concept of neuroinflammation. We then discuss the contribution of P2X, P2Y and P1 receptors to the underlying processes, including a discussion of cross-talk between these different pathways. Finally, we give an overview of the current understanding of purinergic contributions to neuroinflammation in the context of specific disorders of the central nervous system, with special emphasis on neuropsychiatric disorders, characterized by chronic low grade inflammation or maternal inflammation. An understanding of the important purinergic contribution to neuroinflammation underlying neuropathology is likely to be a necessary step towards the development of effective interventions.
This article is part of the Special Issue entitled ‘Purines in Neurodegeneration and Neuroregeneration’.
•Purines are released to the extracellular space under neuroinflammation.•Adenosine and ATP both activate inflammasome via purinergic receptors.•P1 and P2 receptors regulate the inflammatory response of the CNS in a complex way.•Purinergic signalling dynamically changes during acute and chronic neuroinflammation.•Changes in purinergic control of inflammation might underlie psychiatric disorders.