title: Fractalkine in the nervous system: neuroprotective or neurotoxic molecule?
abstract: Fractalkine (CX3CL1) is an intriguing chemokine that plays a central role in the nervous system. The expression of CX3CL1 on neurons and of its receptor CX3CR1 on microglia facilitates a privileged interaction, playing important roles in regulating the function and maturation of these cells. CX3CL1 is reported to have neuroprotective and anti-inflammatory activities in several experimental systems and animal models of disease, and its expression correlates with positive outcomes in human neuropathologies. However, a comparable amount of evidence shows that CX3CL1 sustains neuroinflammatory conditions and contributes to neurotoxicity. This review discusses the evidence in favor of the CX3CL1/CX3CR1 pair being neuroprotective and other evidence that it is neurotoxic. Our aim is to stimulate future research examining the molecular and cellular determinants responsible for this unique functional switch, which could be important for several neuropathologies.
authors.affiliation: Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Lauro
authors.affiliation: Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.|IRCCS NeuroMed, Pozzilli, Italy.
authors.forename: Myriam
authors.initials: M
authors.lastname: Catalano
authors.affiliation: Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Trettel
authors.affiliation: Department of Physiology and Pharmacology, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.|IRCCS NeuroMed, Pozzilli, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Limatola
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D001921:Brain / Q000276:immunology*; D001927:Brain Diseases / Q000276:immunology / Q000503:physiopathology*; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1 / Q000096:biosynthesis / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000276:immunology; D017628:Microglia / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D018696:Neuroprotective Agents; D019707:Receptors, Chemokine
keywords: brain disease; fractalkine; inflammation; microglia; neuroprotection