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 (Glu)-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 cyclic-AMP response element-binding protein (CREB) phosphorylation.
Fractalkine/CX3CL1 engages different neuroprotective responses upon selective glutamate receptor overactivation / C. Lauro, M. Catalano, E. Di Paolo, G. Chece, I. de Costanzo, F. Trettel, C. Limatola. - In: FRONTIERS IN CELLULAR NEUROSCIENCE. - ISSN 1662-5102. - 8(2015 Jan 21), pp. 472.1-472.8.
|Titolo:||Fractalkine/CX3CL1 engages different neuroprotective responses upon selective glutamate receptor overactivation|
|Parole Chiave:||A2AR; CX3CL1; D-serine; NMDA; excitotoxicity; neuroprotection; cellular and molecular neuroscience|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||21-gen-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3389/fncel.2014.00472|
|Appare nelle tipologie:||01 - Articolo su periodico|