P2Y12 Receptor on the Verge of a Neuroinflammatory Breakdown
In the CNS, neuroinflammation occurring during pathologies as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) is the consequence of an intricate interplay orchestrated by various cell phenotypes. Among the molecular cues having a role in this process, extracellular nucleotides are re...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/975849 |
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| author | Susanna Amadio Chiara Parisi Cinzia Montilli Alberto Savio Carrubba Savina Apolloni Cinzia Volonté |
| author_facet | Susanna Amadio Chiara Parisi Cinzia Montilli Alberto Savio Carrubba Savina Apolloni Cinzia Volonté |
| author_sort | Susanna Amadio |
| collection | DOAJ |
| description | In the CNS, neuroinflammation occurring during pathologies as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) is the consequence of an intricate interplay orchestrated by various cell phenotypes. Among the molecular cues having a role in this process, extracellular nucleotides are responsible for intercellular communication and propagation of inflammatory stimuli. This occurs by binding to several receptor subtypes, defined P2X/P2Y, which are widespread in different tissues and simultaneously localized on multiple cells. For instance, the metabotropic P2Y12 subtype is found in the CNS on microglia, affecting activation and chemotaxis, on oligodendrocytes, possessing a hypothesized role in myelination, and on astrocytes. By comparative analysis, we have established here that P2Y12 receptor immunolabelled by antibodies against C-terminus or second intracellular loop, is, respectively, distributed and modulated under neuroinflammatory conditions on ramified microglia or myelinated fibers, in primary organotypic cerebellar cultures, tissue slices from rat striatum and cerebellum, spinal cord sections from symptomatic/end stage SOD1-G93A ALS mice, and finally autoptic cortical tissue from progressive MS donors. We suggest that modulation of P2Y12 expression might play a dual role as analytic marker of branched/surveillant microglia and demyelinating lesions, thus potentially acquiring a predictive value under neuroinflammatory conditions as those found in ALS and MS. |
| format | Article |
| id | doaj-art-1da9dfa59ee54ee8a1b2472803cc42c2 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1da9dfa59ee54ee8a1b2472803cc42c22025-08-20T03:54:38ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/975849975849P2Y12 Receptor on the Verge of a Neuroinflammatory BreakdownSusanna Amadio0Chiara Parisi1Cinzia Montilli2Alberto Savio Carrubba3Savina Apolloni4Cinzia Volonté5Santa Lucia Foundation, Via del Fosso di Fiorano 65, 00143 Rome, ItalyCellular Biology and Neurobiology Institute (CNR), Via del Fosso di Fiorano 65, 00143 Rome, ItalySanta Lucia Foundation, Via del Fosso di Fiorano 65, 00143 Rome, ItalySanta Lucia Foundation, Via del Fosso di Fiorano 65, 00143 Rome, ItalySanta Lucia Foundation, Via del Fosso di Fiorano 65, 00143 Rome, ItalySanta Lucia Foundation, Via del Fosso di Fiorano 65, 00143 Rome, ItalyIn the CNS, neuroinflammation occurring during pathologies as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) is the consequence of an intricate interplay orchestrated by various cell phenotypes. Among the molecular cues having a role in this process, extracellular nucleotides are responsible for intercellular communication and propagation of inflammatory stimuli. This occurs by binding to several receptor subtypes, defined P2X/P2Y, which are widespread in different tissues and simultaneously localized on multiple cells. For instance, the metabotropic P2Y12 subtype is found in the CNS on microglia, affecting activation and chemotaxis, on oligodendrocytes, possessing a hypothesized role in myelination, and on astrocytes. By comparative analysis, we have established here that P2Y12 receptor immunolabelled by antibodies against C-terminus or second intracellular loop, is, respectively, distributed and modulated under neuroinflammatory conditions on ramified microglia or myelinated fibers, in primary organotypic cerebellar cultures, tissue slices from rat striatum and cerebellum, spinal cord sections from symptomatic/end stage SOD1-G93A ALS mice, and finally autoptic cortical tissue from progressive MS donors. We suggest that modulation of P2Y12 expression might play a dual role as analytic marker of branched/surveillant microglia and demyelinating lesions, thus potentially acquiring a predictive value under neuroinflammatory conditions as those found in ALS and MS.http://dx.doi.org/10.1155/2014/975849 |
| spellingShingle | Susanna Amadio Chiara Parisi Cinzia Montilli Alberto Savio Carrubba Savina Apolloni Cinzia Volonté P2Y12 Receptor on the Verge of a Neuroinflammatory Breakdown Mediators of Inflammation |
| title | P2Y12 Receptor on the Verge of a Neuroinflammatory Breakdown |
| title_full | P2Y12 Receptor on the Verge of a Neuroinflammatory Breakdown |
| title_fullStr | P2Y12 Receptor on the Verge of a Neuroinflammatory Breakdown |
| title_full_unstemmed | P2Y12 Receptor on the Verge of a Neuroinflammatory Breakdown |
| title_short | P2Y12 Receptor on the Verge of a Neuroinflammatory Breakdown |
| title_sort | p2y12 receptor on the verge of a neuroinflammatory breakdown |
| url | http://dx.doi.org/10.1155/2014/975849 |
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