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

Tang, Sung-Chun, Arumugam, Thiruma V., Xu, Xiangru, Cheng, Aiwu, Mughal, Mohamed R., Jo, Dong Gyu, Lathia, Justin D., Siler, Dominic A., Chigurupati, Srinivasulu, Ouyang, Xin, Magnus, Tim, Camandola, Simonetta and Mattson, Mark P. (2007) Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proceedings of the National Academy of Sciences of the United States of America, 104 34: 13798-13803. doi:10.1073/pnas.0702553104


Author Tang, Sung-Chun
Arumugam, Thiruma V.
Xu, Xiangru
Cheng, Aiwu
Mughal, Mohamed R.
Jo, Dong Gyu
Lathia, Justin D.
Siler, Dominic A.
Chigurupati, Srinivasulu
Ouyang, Xin
Magnus, Tim
Camandola, Simonetta
Mattson, Mark P.
Title Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2007-08-21
Sub-type Article (original research)
DOI 10.1073/pnas.0702553104
Open Access Status Not Open Access
Volume 104
Issue 34
Start page 13798
End page 13803
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
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-γ 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.
Keyword AP-1
Apoptosis
Innate immunity
Ischemic stroke
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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