• Sung-Chun Tang, Thiruma V Arumugam, Xiangru Xu, Aiwu Cheng, Mohamed R Mughal, Dong Gyu Jo, Justin D Lathia, Dominic A Siler, Srinivasulu Chigurupati, Xin Ouyang, Tim Magnus, Simonetta Camandola, and Mark P Mattson.
• Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA.
• Proc. Natl. Acad. Sci. U.S.A. 2007 Aug 21;104(34):13798-803.

AbstractThe innate immune system senses the invasion of pathogenic microorganisms and tissue injury through Toll-like receptors (TLR), a mechanism thought to be limited to immune cells. We now report that neurons express several TLRs, and that the levels of TLR2 and -4 are increased in neurons in response to IFN-gamma stimulation and energy deprivation. Neurons from both TLR2 knockout and -4 mutant mice were protected against energy deprivation-induced cell death, which was associated with decreased activation of a proapoptotic signaling cascade involving jun N-terminal kinase and the transcription factor AP-1. TLR2 and -4 expression was increased in cerebral cortical neurons in response to ischemia/reperfusion injury, and the amount of brain damage and neurological deficits caused by a stroke were significantly less in mice deficient in TLR2 or -4 compared with WT control mice. Our findings establish a proapoptotic signaling pathway for TLR2 and -4 in neurons that may render them vulnerable to ischemic death.

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