Neuronal death induced by overactivation of N-methyl-d-aspartate receptors (NMDARs) is implicated in the pathophysiology of many neurodegenerative diseases such as stroke, epilepsy and traumatic brain injury. This toxic effect is mainly mediated by NR2B-containing extrasynaptic NMDARs, while NR2A-containing synaptic NMDARs contribute to cell survival, suggesting the possibility of therapeutic approaches targeting specific receptor subunits. We report that fractalkine/CX3CL1 protects hippocampal neurons from NMDA-induced cell death with a mechanism requiring the adenosine receptors type 2A (A2AR). This is different from CX3CL1-induced protection from glutamate-induced cell death, that fully depends on A1R and requires in part A3R. We show that CX3CL1 neuroprotection against NMDA excitotoxicity involves D-serine, a co-agonist of NR2A/NMDAR, resulting in cyclic AMP-dependent transcription factor (CREB) phosphorylation.

Fractalkine/CX3CL1 engages different neuroprotective responses upon selective glutamate receptor overactivation / Lauro, Clotilde; Catalano, Myriam; E., Di Paolo; Chece, Giuseppina; DE COSTANZO, Ida; Trettel, Flavia; Limatola, Cristina. - In: FRONTIERS IN CELLULAR NEUROSCIENCE. - ISSN 1662-5102. - ELETTRONICO. - 8:(2015). [10.3389/fncel.2014.00472]

Fractalkine/CX3CL1 engages different neuroprotective responses upon selective glutamate receptor overactivation

LAURO, CLOTILDE;CATALANO, Myriam;CHECE, Giuseppina;DE COSTANZO, IDA;TRETTEL, Flavia;LIMATOLA, Cristina
2015

Abstract

Neuronal death induced by overactivation of N-methyl-d-aspartate receptors (NMDARs) is implicated in the pathophysiology of many neurodegenerative diseases such as stroke, epilepsy and traumatic brain injury. This toxic effect is mainly mediated by NR2B-containing extrasynaptic NMDARs, while NR2A-containing synaptic NMDARs contribute to cell survival, suggesting the possibility of therapeutic approaches targeting specific receptor subunits. We report that fractalkine/CX3CL1 protects hippocampal neurons from NMDA-induced cell death with a mechanism requiring the adenosine receptors type 2A (A2AR). This is different from CX3CL1-induced protection from glutamate-induced cell death, that fully depends on A1R and requires in part A3R. We show that CX3CL1 neuroprotection against NMDA excitotoxicity involves D-serine, a co-agonist of NR2A/NMDAR, resulting in cyclic AMP-dependent transcription factor (CREB) phosphorylation.
CX3CL1; NMDA; A2AR; d-serine; neuroprotection; excitotoxicity
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Fractalkine/CX3CL1 engages different neuroprotective responses upon selective glutamate receptor overactivation / Lauro, Clotilde; Catalano, Myriam; E., Di Paolo; Chece, Giuseppina; DE COSTANZO, Ida; Trettel, Flavia; Limatola, Cristina. - In: FRONTIERS IN CELLULAR NEUROSCIENCE. - ISSN 1662-5102. - ELETTRONICO. - 8:(2015). [10.3389/fncel.2014.00472]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/664100
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