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Thus, it has been proposed that fractalkine regulates cellular communication between neurons (that produce fractalkine) and microglia (that express its receptor). Here we show, for the first time, that hippocampal neurons also express CX<jats:sub>3<\/jats:sub>CR1. Receptor activation by soluble fractalkine induces activation of the protein kinase Akt, a major component of prosurvival signaling pathways, and nuclear translocation of NF-\u03baB, a downstream effector of Akt. Fractalkine protects hippocampal neurons from the neurotoxicity induced by the HIV-1 envelope protein gp120<jats:sub>IIIB<\/jats:sub>, an effect blocked by anti-CX<jats:sub>3<\/jats:sub>CR1 antibodies. Experiments with two different inhibitors of the phosphatidylinositol 3-kinase, a key enzyme in the activation of Akt, and with a phospholipid activator of Akt demonstrate that Akt activation is responsible for the neuroprotective effects of fractalkine. These data show that neuronal CX<jats:sub>3<\/jats:sub>CR1 receptors mediate the neurotrophic effects of fractalkine, suggesting that fractalkine and its receptor are involved in a complex network of both paracrine and autocrine interactions between neurons and glia.<\/jats:p>","DOI":"10.1073\/pnas.090017497","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:32:33Z","timestamp":1027693953000},"page":"8075-8080","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":318,"title":["Expression of CX<sub>3<\/sub>CR1 chemokine receptors on neurons and their role in neuronal survival"],"prefix":"10.1073","volume":"97","author":[{"given":"Olimpia","family":"Meucci","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Pharmacology, and Physiology, and Committee on Neurobiology, University of Chicago, Chicago, IL 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