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Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13798-803. Epub 2007 Aug 10.

Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits.

Author information

1
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA.

Abstract

The 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.

PMID:
17693552
PMCID:
PMC1959462
DOI:
10.1073/pnas.0702553104
[Indexed for MEDLINE]
Free PMC Article

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