Control of microglial neurotoxicity by the fractalkine receptor

被引：1178

作者：

Cardona, Astrid E.

Pioro, Erik P.

Sasse, Margaret E.

Kostenko, Volodymyr

Cardona, Sandra M.

Dijkstra, Ineke M.

Huang, DeRen

Kidd, Grahame

Dombrowski, Stephen

Dutta, RanJan

Lee, Jar-Chi

Cook, Donald N.

Jung, Steffen

Lira, Sergio A.

Littman, Dan R.

Ransohoff, Richard M. ^{[1
]}

机构：

[1] Cleveland Clin, Neuroinflammat Res Ctr, Cleveland, OH 44195 USA

[2] Cleveland Clin, Dept Neurosci, Lerner Res Inst, Cleveland, OH 44195 USA

[3] Cleveland Clin, Dept Neurosurg, Cleveland, OH 44195 USA

[4] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA

[5] NIEHS, Res Triangle Pk, NC 27709 USA

[6] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel

[7] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA

[8] NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA

[9] Mt Sinai Sch Med, Immunobiol Ctr, New York, NY 10029 USA

来源：

NATURE NEUROSCIENCE | 2006年 / 9卷 / 07期

关键词：

D O I：

10.1038/nn1715

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Microglia, the resident inflammatory cells of the CNS, are the only CNS cells that express the fractalkine receptor ( CX3CR1). Using three different in vivo models, we show that CX3CR1 deficiency dysregulates microglial responses, resulting in neurotoxicity. Following peripheral lipopolysaccharide injections, Cx3cr1(-/-) mice showed cell-autonomous microglial neurotoxicity. In a toxic model of Parkinson disease and a transgenic model of amyotrophic lateral sclerosis, Cx3cr1(-/-) mice showed more extensive neuronal cell loss than Cx3cr(+) littermate controls. Augmenting CX3CR1 signaling may protect against microglial neurotoxicity, whereas CNS penetration by pharmaceutical CX3CR1 antagonists could increase neuronal vulnerability.

引用

页码：917 / 924

页数：8

共 39 条

[1] The chemokine fractalkine inhibits Fas-mediated cell death of brain microglia [J].