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

Clotilde Lauro, Myriam Catalano, Eleonora Di Paolo, Giuseppina Chece, Ida de Costanzo, Flavia Trettel, Cristina Limatola

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number472
JournalFrontiers in Cellular Neuroscience
Issue numberJAN
Publication statusPublished - Jan 21 2015


  • A<inf>2A</inf>R
  • CX3CL1
  • D-serine
  • Excitotoxicity
  • Neuroprotection
  • NMDA

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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