title: Purinergic mechanisms in neuroinflammation: An update from molecules to behavior.
abstract: 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'.
authors.affiliation: Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1450 Budapest, Hungary.
authors.forename: Edward
authors.initials: E
authors.lastname: Beamer
authors.affiliation: Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1450 Budapest, Hungary.
authors.forename: Flóra
authors.initials: F
authors.lastname: Gölöncsér
authors.affiliation: Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1450 Budapest, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Horváth
authors.affiliation: Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1450 Budapest, Hungary.
authors.forename: Katinka
authors.initials: K
authors.lastname: Bekő
authors.affiliation: Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1450 Budapest, Hungary.
authors.forename: Lilla
authors.initials: L
authors.lastname: Otrokocsi
authors.affiliation: Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1450 Budapest, Hungary.
authors.forename: Bence
authors.initials: B
authors.lastname: Koványi
authors.affiliation: Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1450 Budapest, Hungary. Electronic address: sperlagh@koki.hu.
authors.forename: Beáta
authors.initials: B
authors.lastname: Sperlágh
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004660:Encephalitis / Q000151:congenital / Q000378:metabolism*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D018836:Inflammation Mediators; D020239:Receptor Cross-Talk; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D058847:Inflammasomes; D018836:Inflammation Mediators; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D000241:Adenosine
keywords: Cytokines; NLRP3 inflammasome; Neuroinflammation; P1 receptor; P2X receptor; P2Y receptor