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P2X7 Receptor Blockade Prevents ATP Excitotoxicity in Oligodendrocytes and Ameliorates Experimental Autoimmune Encephalomyelitis
Oligodendrocyte death and demyelination are hallmarks of multiple sclerosis (MS). Here we show that ATP signaling can trigger oligodendrocyte excitotoxicity via activation of calcium-permeable P2X 7 purinergic receptors expressed by these cells. Sustained activation of P2X 7 receptors in vivo causes...
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| Published in: | The Journal of neuroscience 2007-08, Vol.27 (35), p.9525-9533 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Article |
| Language: | English |
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| container_end_page | 9533 |
| container_issue | 35 |
| container_start_page | 9525 |
| container_title | The Journal of neuroscience |
| container_volume | 27 |
| creator | Matute, Carlos Torre, Iratxe Perez-Cerda, Fernando Perez-Samartin, Alberto Alberdi, Elena Etxebarria, Estibaliz Arranz, Amaia M Ravid, Rivka Rodriguez-Antiguedad, Alfredo Sanchez-Gomez, MariaVictoria Domercq, Maria |
| description | Oligodendrocyte death and demyelination are hallmarks of multiple sclerosis (MS). Here we show that ATP signaling can trigger oligodendrocyte excitotoxicity via activation of calcium-permeable P2X
7
purinergic receptors expressed by these cells. Sustained activation of P2X
7
receptors
in vivo
causes lesions that are reminiscent of the major features of MS plaques, i.e., demyelination, oligodendrocyte death, and axonal damage. In addition, treatment with P2X
7
antagonists of chronic experimental autoimmune encephalomyelitis (EAE), a model of MS, reduces demyelination and ameliorates the associated neurological symptoms. Together, these results indicate that ATP can kill oligodendrocytes via P2X
7
activation and that this cell death process contributes to EAE. Importantly, P2X
7
expression is elevated in normal-appearing axon tracts in MS patients, suggesting that signaling through this receptor in oligodendrocytes may be enhanced in this disease. Thus, P2X
7
receptor antagonists may be beneficial for the treatment of MS. |
| doi_str_mv | 10.1523/JNEUROSCI.0579-07.2007 |
| format | article |
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7
purinergic receptors expressed by these cells. Sustained activation of P2X
7
receptors
in vivo
causes lesions that are reminiscent of the major features of MS plaques, i.e., demyelination, oligodendrocyte death, and axonal damage. In addition, treatment with P2X
7
antagonists of chronic experimental autoimmune encephalomyelitis (EAE), a model of MS, reduces demyelination and ameliorates the associated neurological symptoms. Together, these results indicate that ATP can kill oligodendrocytes via P2X
7
activation and that this cell death process contributes to EAE. Importantly, P2X
7
expression is elevated in normal-appearing axon tracts in MS patients, suggesting that signaling through this receptor in oligodendrocytes may be enhanced in this disease. Thus, P2X
7
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7
purinergic receptors expressed by these cells. Sustained activation of P2X
7
receptors
in vivo
causes lesions that are reminiscent of the major features of MS plaques, i.e., demyelination, oligodendrocyte death, and axonal damage. In addition, treatment with P2X
7
antagonists of chronic experimental autoimmune encephalomyelitis (EAE), a model of MS, reduces demyelination and ameliorates the associated neurological symptoms. Together, these results indicate that ATP can kill oligodendrocytes via P2X
7
activation and that this cell death process contributes to EAE. Importantly, P2X
7
expression is elevated in normal-appearing axon tracts in MS patients, suggesting that signaling through this receptor in oligodendrocytes may be enhanced in this disease. Thus, P2X
7
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7
purinergic receptors expressed by these cells. Sustained activation of P2X
7
receptors
in vivo
causes lesions that are reminiscent of the major features of MS plaques, i.e., demyelination, oligodendrocyte death, and axonal damage. In addition, treatment with P2X
7
antagonists of chronic experimental autoimmune encephalomyelitis (EAE), a model of MS, reduces demyelination and ameliorates the associated neurological symptoms. Together, these results indicate that ATP can kill oligodendrocytes via P2X
7
activation and that this cell death process contributes to EAE. Importantly, P2X
7
expression is elevated in normal-appearing axon tracts in MS patients, suggesting that signaling through this receptor in oligodendrocytes may be enhanced in this disease. Thus, P2X
7
receptor antagonists may be beneficial for the treatment of MS.</abstract><pub>Soc Neuroscience</pub><pmid>17728465</pmid><doi>10.1523/JNEUROSCI.0579-07.2007</doi><tpages>9</tpages></addata></record> |
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| title | P2X7 Receptor Blockade Prevents ATP Excitotoxicity in Oligodendrocytes and Ameliorates Experimental Autoimmune Encephalomyelitis |
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