Extracellular nucleotides as danger signals in the CNS: new perspectives for brain repair

Abstract

Event Abstract Back to Event Extracellular nucleotides as danger signals in the CNS: new perspectives for brain repair Maria P. Abbracchio1* 1 University of Milan, Department of Pharmacological Sciences, Italy In the CNS, depending upon specific acute or chronic pathological conditions, both protective and detrimental actions have been repeatedly reported for extracellular nucleosides and nucleotides and for their receptors: the P1/adenosine and the P2/nucleotide receptors. Recent data have shed light on these apparently contrasting data. An emerging hypothesis suggests that, in a similar way to the immune system, in both brain and spinal cord, under disease conditions (e.g., hypoxia/trauma), extracellularly-released nucleotides may act as diffusible danger signals to alert surrounding cells, activate beneficial inflammation and start repair. These emergency signals are sensed by target cells via purinergic receptors. However, if inappropriately sustained and excessively prolonged in time, danger signals become detrimental, and eventually contribute to neuronal death. In line with this hypothesis, selected P2X/P2Y antagonists reduced brain damage in various in vitro and in vivo neurodegeneration models (Franke et al., Pflugers Arch. 452:622-44, 2006). In this respect, we have recently identified a new purinergic receptor likely playing a prominent role in ischemia-associated damage. This receptor (GPR17) is dually activated by uracil nucleotides and cysteinyl-leucotrienes, a chemically-unrelated, arachidonic acid-derived, family of inflammatory mediators which are also released in the ischemic brain (Ciana et al., EMBOJ, 25:4615-27, 2006). Blockade of GPR17 by a pharmacological or an anti-sense strategy markedly reduced the propagation of acute ischemic damage (see also: Lecca et al., PLoS ONE, 2008;3(10):e3579). We have recently confirmed a potential role for GPR17 in the neurodegeneration associated to spinal cord injury (SCI, Villa et al., submitted for publication). Of high interest for neuroreparative events, in both brain and spinal cord, GPR17 was also found on microglial/macrophages migrating to the injured area to start remodeling, and on adult endogenous neural stem cells, where it may participate to the post-injury generation of newborn neurons and oligodendrocytes. Thus, the acute over-activation of GPR17 during ischemia or SCI may contribute to damage; conversely, presence of GPR17 on microglia and neuroprogenitor-like cells also suggests a role in the long-term reparative changes associated to these conditions. Keywords: danger signal, Extracellular nucleotides, P2 receptors, post-injury repair, sensor of damage Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009. Presentation Type: Oral Presentation Topic: Symposium 27 – The purinergic system as a target for the development of novel drugs for acute and chronic CNS disorders Citation: Abbracchio MP (2009). Extracellular nucleotides as danger signals in the CNS: new perspectives for brain repair. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.096 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 20 Nov 2009; Published Online: 20 Nov 2009. * Correspondence: Maria P Abbracchio, University of Milan, Department of Pharmacological Sciences, Milan, Italy, mariapia.abbracchio@unimi.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Maria P Abbracchio Google Maria P Abbracchio Google Scholar Maria P Abbracchio PubMed Maria P Abbracchio Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.